Submissions for variant NM_000257.4(MYH7):c.5587C>T (p.Arg1863Trp)

gnomAD frequency: 0.00001  dbSNP: rs376668612

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001175712	SCV001339421	uncertain significance	Cardiomyopathy	2023-02-02	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with tryptophan at codon 1863 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 hypertrophic cardiomyopathy (PMID: 27532257). This variant has been identified in 2/251042 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	RCV001875781	SCV002121222	uncertain significance	Hypertrophic cardiomyopathy	2023-05-01	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 918220). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). This variant is present in population databases (rs376668612, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1863 of the MYH7 protein (p.Arg1863Trp). 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 expected to disrupt MYH7 protein function. 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.
Fulgent Genetics, Fulgent Genetics	RCV002505758	SCV002815403	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	2021-11-15	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003132252	SCV003817763	uncertain significance	not provided	2022-03-23	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001175712	SCV004819606	uncertain significance	Cardiomyopathy	2023-03-09	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with tryptophan at codon 1863 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 hypertrophic cardiomyopathy (PMID: 27532257). This variant has been identified in 2/251042 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.