Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000455842 | SCV000539838 | uncertain significance | not specified | 2016-10-20 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 HCM proband (PMID 22765922), 1 Finnish DCM proband (PMID 26084686); No segregation data; ClinVar: LP by Blueprint |
Color Diagnostics, |
RCV001189904 | SCV001357287 | uncertain significance | Cardiomyopathy | 2023-08-03 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 100 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 26084686). It has also been reported in two unrelated individuals affected with hypertrophic cardiomyopathy who both carried additional pathogenic variants (PMID: 22765922, 23396983, 23870641, 25351510, 26654849, 27532257, 28356264). This variant has been identified in 4/251476 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001850185 | SCV002264840 | uncertain significance | Hypertrophic cardiomyopathy | 2022-03-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 180430). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 22765922, 27532257). This variant is present in population databases (rs730880154, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 100 of the MYH7 protein (p.Ala100Thr). |
Ambry Genetics | RCV002433691 | SCV002751458 | uncertain significance | Cardiovascular phenotype | 2020-12-22 | criteria provided, single submitter | clinical testing | The p.A100T variant (also known as c.298G>A), located in coding exon 2 of the MYH7 gene, results from a G to A substitution at nucleotide position 298. The alanine at codon 100 is replaced by threonine, an amino acid with similar properties. This variant has been detected in hypertrophic cardiomyopathy cohorts; however, case reports may overlap and some individuals also had mutations other cardiomyopathy-related genes (Coto E et al. J Mol Diagn, 2012 Sep;14:518-24; Reguero JR et al. Int J Cardiol, 2013 Oct;168:4555-6; Lopes LR et al. J Med Genet, 2013 Apr;50:228-39; Lopes LR et al. Heart, 2015 Feb;101:294-301; Gómez J et al. Rev Esp Cardiol (Engl Ed), 2016 Jan;69:61-8; Walsh R et al. Genet Med, 2017 02;19:192-203). This variant has also been detected in an individual from a dilated cardiomyopathy cohort; however, details were limited (Akinrinade O et al. Eur Heart J, 2015 Sep;36:2327-37). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Blueprint Genetics | RCV000157347 | SCV000207084 | likely pathogenic | Restrictive cardiomyopathy | 2014-07-03 | no assertion criteria provided | clinical testing |