ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5071G>A (p.Val1691Met)

gnomAD frequency: 0.00011  dbSNP: rs45464193
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208343 SCV000264096 uncertain significance Left ventricular noncompaction cardiomyopathy 2015-05-25 criteria provided, single submitter clinical testing
GeneDx RCV001722137 SCV000565697 uncertain significance not provided 2021-09-07 criteria provided, single submitter clinical testing Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 222731; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27247418, 20800588, 23403236, 19412328, 12707239)
Invitae RCV000531386 SCV000623733 uncertain significance Hypertrophic cardiomyopathy 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1691 of the MYH7 protein (p.Val1691Met). This variant is present in population databases (rs45464193, gnomAD 0.02%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy and dilated cardiomyopathy (PMID: 12707239, 19412328, 27247418). ClinVar contains an entry for this variant (Variation ID: 222731). 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 not expected to disrupt MYH7 protein function with a negative 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769438 SCV000900831 uncertain significance Cardiomyopathy 2019-06-11 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769438 SCV001355410 uncertain significance Cardiomyopathy 2023-04-07 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 1691 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 been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 12707239) and in an individual affected with dilated cardiomyopathy (PMID: 19412328). This variant has been identified in 16/282712 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 RCV002347814 SCV002645951 uncertain significance Cardiovascular phenotype 2019-09-09 criteria provided, single submitter clinical testing The p.V1691M variant (also known as c.5071G>A), located in coding exon 33 of the MYH7 gene, results from a G to A substitution at nucleotide position 5071. The valine at codon 1691 is replaced by methionine, an amino acid with highly similar properties. This variant has been detected in individuals from hypertrophic cardiomypathy and dilated cardiomyopathy cohorts; however, clinical details were limited (Richard P et al. Circulation, 2003 May;107:2227-32; Hershberger RE et al. Clin Transl Sci, 2008 May;1:21-6). This variant has also been detected in genome sequencing and population-based cohorts in individuals not indicated as having overt cardiomyopathy (Bick AG et al. Am. J. Hum. Genet., 2012 Sep;91:513-9; Kwak SH et al. Exp. Mol. Med., 2017 07;49:e356). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001722137 SCV003817736 uncertain significance not provided 2022-09-22 criteria provided, single submitter clinical testing

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