Submissions for variant NM_000257.4(MYH7):c.50G>A (p.Arg17His)

gnomAD frequency: 0.00001  dbSNP: rs727503280

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151316	SCV000199281	uncertain significance	not specified	2014-02-17	criteria provided, single submitter	clinical testing	The Arg17His variant in MYH7 has not been previously reported in individuals wit h cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, thou gh this information is not predictive enough to determine pathogenicity. Additio nal information is needed to fully assess the clinical significance of the Arg17 His variant.
CeGaT Center for Human Genetics Tuebingen	RCV001093026	SCV001249815	uncertain significance	not provided	2020-03-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001185781	SCV001352072	uncertain significance	Cardiomyopathy	2023-06-09	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 17 of the MYH7 protein. This variant is found within a highly conserved region of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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 one individual affected with hypertrophic cardiomyopathy (PMID: 25351510). This variant has been identified in 1/251366 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	RCV001338885	SCV001532590	uncertain significance	Hypertrophic cardiomyopathy	2022-07-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 17 of the MYH7 protein (p.Arg17His). This variant is present in population databases (rs727503280, gnomAD 0.0009%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25351510). ClinVar contains an entry for this variant (Variation ID: 164407). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV001093026	SCV002496429	uncertain significance	not provided	2022-03-10	criteria provided, single submitter	clinical testing
AiLife Diagnostics, AiLife Diagnostics	RCV001093026	SCV002501805	uncertain significance	not provided	2021-07-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345473	SCV002645803	uncertain significance	Cardiovascular phenotype	2019-04-27	criteria provided, single submitter	clinical testing	The p.R17H variant (also known as c.50G>A), located in coding exon 1 of the MYH7 gene, results from a G to A substitution at nucleotide position 50. The arginine at codon 17 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.