ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4216G>A (p.Val1406Met)

gnomAD frequency: 0.00006  dbSNP: rs201566738
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000816147 SCV000956640 uncertain significance Hypertrophic cardiomyopathy 14 2023-11-28 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 1406 of the MYH6 protein (p.Val1406Met). This variant is present in population databases (rs201566738, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 28416588). ClinVar contains an entry for this variant (Variation ID: 180426). 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 MYH6 protein function with a negative predictive value of 80%. 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 RCV001529781 SCV001792052 uncertain significance not provided 2024-07-22 criteria provided, single submitter clinical testing Reported in at least one patient with dilated cardiomyopathy (PMID: 28416588, 31514951); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31514951, 28416588)
Ambry Genetics RCV002326894 SCV002630088 uncertain significance Cardiovascular phenotype 2022-06-02 criteria provided, single submitter clinical testing The p.V1406M variant (also known as c.4216G>A), located in coding exon 28 of the MYH6 gene, results from a G to A substitution at nucleotide position 4216. The valine at codon 1406 is replaced by methionine, an amino acid with highly similar properties. This variant has been detected in a dilated cardiomyopathy cohort; however, details were limited (Gigli M et al. J Am Coll Cardiol, 2019 09;74:1480-1490). This amino acid position is well 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.
Breakthrough Genomics, Breakthrough Genomics RCV001529781 SCV005192257 uncertain significance not provided criteria provided, single submitter not provided
Blueprint Genetics RCV000157340 SCV000207077 uncertain significance Primary dilated cardiomyopathy 2014-09-29 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001529781 SCV001743851 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001529781 SCV001956934 uncertain significance not provided no assertion criteria provided clinical testing

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