Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000725808 | SCV000237226 | likely benign | not provided | 2021-04-30 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26272908, 23396983) |
Invitae | RCV001082934 | SCV000286689 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-08 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000725808 | SCV000701146 | uncertain significance | not provided | 2017-11-17 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000591920 | SCV000710956 | uncertain significance | not specified | 2016-04-25 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Asp13432His v ariant in TTN has not been previously reported in individuals with cardiomyopath y, but has been identified in 0.18% (117/66584) of European chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs20138 8509). Computational prediction tools and conservation analysis do not provide s trong support for or against an impact to the protein. In summary, while the cli nical significance of the p.Asp13432His variant is uncertain, its frequency sugg ests that it is more likely to be benign. |
Ambry Genetics | RCV000621855 | SCV000736925 | likely benign | Cardiovascular phenotype | 2020-04-03 | 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, |
RCV001128984 | SCV001288480 | uncertain significance | Early-onset myopathy with fatal cardiomyopathy | 2018-01-12 | 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, |
RCV001128985 | SCV001288481 | uncertain significance | Dilated cardiomyopathy 1G | 2018-01-12 | 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, |
RCV001128986 | SCV001288482 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-01-12 | 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, |
RCV001128987 | SCV001288483 | benign | Tibial muscular dystrophy | 2018-01-12 | 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, |
RCV001128988 | SCV001288484 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 2018-01-12 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000591920 | SCV002600797 | likely benign | not specified | 2022-10-28 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.40294G>C (p.Asp13432His) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00085 in 247398 control chromosomes. The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is benign. c.40294G>C has been reported in the literature in one infant with SIDS (Santori_2015) and two individuals with Hypertrophic Cardiomyopathy (Lopes_2013) without strong evidence for causality in all instances. These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. These laboratories classified as VUS (n=3), likely benign (n=3) and benign (n=1) . Based on the evidence outlined above, the variant was classified as likely benign. |
Ce |
RCV000725808 | SCV003916190 | likely benign | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | TTN: BP4 |
Prevention |
RCV004537546 | SCV004725855 | likely benign | TTN-related disorder | 2022-05-02 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Diagnostic Laboratory, |
RCV000725808 | SCV001742932 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000725808 | SCV001797819 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000591920 | SCV001917420 | benign | not specified | no assertion criteria provided | clinical testing |