Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000184654 | SCV000237342 | likely benign | not provided | 2021-02-26 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 30847666, 23396983) |
Illumina Laboratory Services, |
RCV000387758 | SCV000422647 | 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, |
RCV000274852 | SCV000422648 | 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, |
RCV000330015 | SCV000422649 | 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. |
Illumina Laboratory Services, |
RCV000375191 | SCV000422650 | 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, |
RCV000335906 | SCV000422652 | 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. |
Eurofins Ntd Llc |
RCV000184654 | SCV000708682 | uncertain significance | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000765567 | SCV000896882 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002321742 | SCV002607349 | uncertain significance | Cardiovascular phenotype | 2019-01-09 | criteria provided, single submitter | clinical testing | The p.G10401A variant (also known as c.31202G>C), located in coding exon 124 of the TTN gene, results from a G to C substitution at nucleotide position 31202. The glycine at codon 10401 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317135 | SCV004021278 | uncertain significance | not specified | 2023-06-23 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.50693G>C (p.Gly16898Ala) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 (i.e., 38 heterozygotes) in 248508 control chromosomes, predominantly at a frequency of 0.0003 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Cardiomyopathy (0.0003 vs 0.00063), allowing no conclusion about variant significance. c.50693G>C has been reported in the literature in individuals affected with hypertrophic cardiomyopathy (e.g., Lopes_2013, Campuzano_2015, Mademont-Soler_2017, vanLint_2019, Martinez-Barrios) and at least one individual with suspected Brugada syndrome (e.g., Scumaci_2018), however without strong evidence for causality in all cases (e.g., lack of co-segregation and co-occurrence data). These reports therefore do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. A co-occurrence with another pathogenic variant was reported (MYBPC3 c.2373_2374insG, p.W792VfsX41; Lopes_2013), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26516846, 23396983, 28771489, 35207729, 29956481, 30847666). Six submitters have reported clinical-significance assessments for this variant to ClinVar after 2014 with conflicting assessments (VUS, n = 4; likely benign, n = 1; benign, n = 1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Diagnostic Laboratory, |
RCV000184654 | SCV001744674 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000184654 | SCV001975844 | uncertain significance | not provided | no assertion criteria provided | clinical testing |