Submissions for variant NM_000257.4(MYH7):c.4901G>A (p.Arg1634His)

dbSNP: rs545875689

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000208188	SCV000264095	uncertain significance	Primary familial hypertrophic cardiomyopathy	2015-01-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000628959	SCV000749868	uncertain significance	Hypertrophic cardiomyopathy	2022-07-29	criteria provided, single submitter	clinical testing	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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 222730). 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). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1634 of the MYH7 protein (p.Arg1634His).
Color Diagnostics, LLC DBA Color Health	RCV001178631	SCV001343130	uncertain significance	Cardiomyopathy	2023-07-25	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 1634 of the MYH7 protein. Computational prediction suggests that this variant may have a 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: 30775854). This variant has been identified in 1/251442 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.
Baylor Genetics	RCV001329733	SCV001521253	uncertain significance	Dilated cardiomyopathy 1S	2019-08-30	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001788068	SCV002030990	uncertain significance	not provided	2021-11-22	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
AiLife Diagnostics, AiLife Diagnostics	RCV001788068	SCV002501202	uncertain significance	not provided	2022-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336579	SCV002635824	uncertain significance	Cardiovascular phenotype	2020-10-13	criteria provided, single submitter	clinical testing	The p.R1634H variant (also known as c.4901G>A), located in coding exon 32 of the MYH7 gene, results from a G to A substitution at nucleotide position 4901. The arginine at codon 1634 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002503822	SCV002814452	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	2021-08-13	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001788068	SCV003817758	uncertain significance	not provided	2022-01-03	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001178631	SCV004826397	uncertain significance	Cardiomyopathy	2023-12-13	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 1634 of the MYH7 protein. Computational prediction suggests that this variant may have a 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: 30775854). This variant has been identified in 1/251442 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.