Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000995347 | SCV000233721 | likely benign | not provided | 2021-09-16 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26188975, 26787436, 28655553, 34426522) |
Ambry Genetics | RCV000247580 | SCV000317911 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2022-12-28 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Illumina Laboratory Services, |
RCV000377435 | SCV000392643 | benign | Ectopia lentis 1, isolated, autosomal dominant | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Illumina Laboratory Services, |
RCV000289798 | SCV000392644 | benign | Acromicric dysplasia | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Illumina Laboratory Services, |
RCV000347117 | SCV000392645 | benign | Geleophysic dysplasia | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Illumina Laboratory Services, |
RCV000407491 | SCV000392646 | likely benign | Marfan syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Illumina Laboratory Services, |
RCV000288772 | SCV000392647 | benign | Stiff skin syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Illumina Laboratory Services, |
RCV000247580 | SCV000392648 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV000407488 | SCV000392649 | likely benign | Weill-Marchesani syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Labcorp Genetics |
RCV000461203 | SCV000544950 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2024-01-11 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000247580 | SCV000904513 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2020-04-20 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000995347 | SCV001149465 | uncertain significance | not provided | 2016-10-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000181419 | SCV001361427 | likely benign | not specified | 2019-03-31 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.902G>T (p.Gly301Val) results in a non-conservative amino acid change located in the EGF-like domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 277146 control chromosomes, predominantly at a frequency of 0.00036 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in FBN1 causing Marfan Syndrome phenotype (0.00011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.902G>T has been reported in the literature in individuals affected with Marfan Syndrome, vascular anomalies and ascending aortic aneurysm (Mattassi_2018, Franken_2016, Ziganshin_2015). These reports do not provide unequivocal conclusions about association of the variant with Marfan Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) classify the variant as likely benign (1x) and uncertain significance (4x). Based on the evidence outlined above, the variant was classified as likely benign. |
Laboratory for Molecular Medicine, |
RCV000181419 | SCV001365724 | uncertain significance | not specified | 2019-01-02 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Identified in 2 Marfan probands (PubMed: 26787436). Computational tools predict benign. Identified in 0.04% of European chromosoems in gnomAD. |
Mayo Clinic Laboratories, |
RCV000995347 | SCV001714519 | uncertain significance | not provided | 2019-09-23 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000995347 | SCV002049917 | uncertain significance | not provided | 2022-04-13 | criteria provided, single submitter | clinical testing | The FBN1 c.902G>T, p.Gly301Val variant (rs142888621; ClinVar variation ID: 199960), has been detected in three patient cohorts composed of Marfan, vascular anomaly, TAAD patients (Franken 2016, Mattassi 2018, Ziganshin 2015); however, direct evidence of pathogenicity is not provided. This variant is found in the general population with an overall allele frequency of 0.02% (51/282,816 alleles) in the Genome Aggregation Database. The glycine at codon 301 is located in the second EGF domain, though is not considered a consensus residue. Overall, this residue is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.372). Based on the available information, the clinical significance of this variant is uncertain. References: Franken et al. Genotype impacts survival in Marfan syndrome. Eur Heart J. 2016 Nov 14;37(43):3285-3290. PMID: 26787436 Mattassi et al. Variant discovery in patients with Mendelian vascular anomalies by next-generation sequencing and their use in patient clinical management. J Vasc Surg. 2018 Mar;67(3):922-932. PMID: 28655553 Ziganshin et al. Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting. Ann Thorac Surg. 2015 Nov;100(5):1604-11. PMID: 26188975 |
CHEO Genetics Diagnostic Laboratory, |
RCV000247580 | SCV003837689 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2021-10-28 | criteria provided, single submitter | clinical testing | |
Center for Genomics, |
RCV003224198 | SCV003919947 | uncertain significance | Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome | 2022-07-26 | criteria provided, single submitter | clinical testing | This variant has been reported in the literature in at least four individuals with various phenotypes including Marfan syndrome, thoracic aortic aneurysm and dissection, and vascular anomalies (Ziganshin 2015 PMID:26188975; Franken 2016 PMID:26787436; Mattassi 2017 PMID:28655553). This variant is present in the Genome Aggregation Database (Highest reported MAF: 0.035% [45/129138]; https://gnomad.broadinstitute.org/variant/15-48818413-C-A?dataset=gnomad_r2_1). This variant is also present in ClinVar (Variation ID:199960). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Center for Medical Genetics Ghent, |
RCV000407491 | SCV000787429 | uncertain significance | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |