Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000435665 | SCV000518921 | uncertain significance | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | Identified in at least one individual with HCM (Garcia-Castro et al., 2009; Coto et al., 2012; Gomez et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24510615, 25342278, 22765922, 19150014, 34542152) |
Invitae | RCV000548210 | SCV000623637 | uncertain significance | Hypertrophic cardiomyopathy | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 4 of the MYH7 protein (p.Ser4Leu). This variant is present in population databases (rs758659692, gnomAD 0.009%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 19150014, 22765922, 25342278). ClinVar contains an entry for this variant (Variation ID: 380650). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH7 protein function with a negative predictive value of 95%. 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. |
Color Diagnostics, |
RCV001524329 | SCV001734133 | uncertain significance | Cardiomyopathy | 2023-01-27 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 4 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 individuals affected with hypertrophic cardiomyopathy (PMID: 19150014, 22765922, 25342278, 28356264). This variant has been identified in 7/250976 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282140 | SCV002570551 | uncertain significance | not specified | 2022-07-19 | criteria provided, single submitter | clinical testing | Variant summary: MYH7 c.11C>T (p.Ser4Leu) results in a non-conservative amino acid change in 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 2.8e-05 in 250976 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.11C>T has been reported in the literature in settings of multigene panel /MYH7 specific testing among cohorts of individuals with Hypertrophic Cardiomyopathy reported as having no family history of HCM and/or hypertrophy (example, Garcio-Castro_2009, Coto_2012, Gomez_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Revvity Omics, |
RCV000435665 | SCV003817682 | uncertain significance | not provided | 2023-11-28 | criteria provided, single submitter | clinical testing |