Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154775 | SCV000204455 | uncertain significance | not specified | 2014-07-14 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001184480 | SCV001350454 | uncertain significance | Cardiomyopathy | 2024-03-06 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 638 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 1/251420 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. |
Labcorp Genetics |
RCV001365021 | SCV001561243 | uncertain significance | Hypertrophic cardiomyopathy | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 638 of the MYH7 protein (p.Ala638Val). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH7 protein function. ClinVar contains an entry for this variant (Variation ID: 178083). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). |
Fulgent Genetics, |
RCV002483343 | SCV002794398 | uncertain significance | Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy | 2021-08-19 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV001184480 | SCV004822516 | uncertain significance | Cardiomyopathy | 2023-11-30 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 638 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 1/251420 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. |
Ambry Genetics | RCV005372245 | SCV006040992 | uncertain significance | Cardiovascular phenotype | 2025-01-03 | criteria provided, single submitter | clinical testing | The p.A638V variant (also known as c.1913C>T), located in coding exon 15 of the MYH7 gene, results from a C to T substitution at nucleotide position 1913. The alanine at codon 638 is replaced by valine, an amino acid with similar properties. This variant has been reported in association with hypertrophic cardiomyopathy (HCM) (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 Jun;113:6701-6). This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |