Submissions for variant NM_000257.4(MYH7):c.3479A>G (p.Gln1160Arg)

gnomAD frequency: 0.00002  dbSNP: rs1376667533

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000701737	SCV000830551	uncertain significance	Hypertrophic cardiomyopathy	2024-09-29	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1160 of the MYH7 protein (p.Gln1160Arg). This variant is present in population databases (no rsID available, gnomAD 0.001%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy and sudden cardiac arrest (PMID: 24111713, 30403391). ClinVar contains an entry for this variant (Variation ID: 578660). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYH7 protein function with a positive 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.
GeneDx	RCV001766540	SCV002008501	uncertain significance	not provided	2022-09-12	criteria provided, single submitter	clinical testing	Reported in patients with hypertrophic cardiomyopathy (HCM) referred for genetic testing at GeneDx and in published literature (Berge et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30403391, 24111713, 34542152)
Color Diagnostics, LLC DBA Color Health	RCV003532247	SCV004356866	uncertain significance	Cardiomyopathy	2024-05-28	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 1160 of the MYH7 protein. Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with hypertrophic cardiomyopathy (PMID: 24111713). This variant has been identified in 1/232242 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.
All of Us Research Program, National Institutes of Health	RCV003532247	SCV004817145	uncertain significance	Cardiomyopathy	2024-09-23	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 1160 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: 24111713). This variant has been identified in 1/232242 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.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV003387913	SCV004099323	uncertain significance	Dilated cardiomyopathy 1S	2023-10-30	no assertion criteria provided	clinical testing