ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4048G>A (p.Glu1350Lys)

gnomAD frequency: 0.00001  dbSNP: rs756392451
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618949 SCV000736883 uncertain significance Cardiovascular phenotype 2020-04-28 criteria provided, single submitter clinical testing The p.E1350K variant (also known as c.4048G>A), located in coding exon 27 of the MYH6 gene, results from a G to A substitution at nucleotide position 4048. The glutamic acid at codon 1350 is replaced by lysine, an amino acid with 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001322419 SCV001513289 uncertain significance Hypertrophic cardiomyopathy 14 2021-10-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1350 of the MYH6 protein (p.Glu1350Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs756392451, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 519019). 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: "Tolerated"; 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.
GeneDx RCV002248817 SCV002520274 uncertain significance not provided 2021-11-23 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 519019; ClinVar); This variant is associated with the following publications: (PMID: 26582918)

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