ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4704C>A (p.Asn1568Lys)

gnomAD frequency: 0.00003  dbSNP: rs149771264
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001373800 SCV001570532 uncertain significance Hypertrophic cardiomyopathy 14 2023-07-29 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1568 of the MYH6 protein (p.Asn1568Lys). This variant is present in population databases (rs149771264, gnomAD 0.02%). 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: 1063911). 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. 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.
Ambry Genetics RCV002341810 SCV002637921 uncertain significance Cardiovascular phenotype 2021-07-26 criteria provided, single submitter clinical testing The p.N1568K variant (also known as c.4704C>A), located in coding exon 31 of the MYH6 gene, results from a C to A substitution at nucleotide position 4704. The asparagine at codon 1568 is replaced by lysine, an amino acid with 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, 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.
PreventionGenetics, part of Exact Sciences RCV004734156 SCV005346297 uncertain significance MYH6-related disorder 2024-06-04 no assertion criteria provided clinical testing The MYH6 c.4704C>A variant is predicted to result in the amino acid substitution p.Asn1568Lys. This variant has been reported in the heterozygous state in an individual with hypertrophic cardiomyopathy; however, this individual also carried additional variants in genes associated with cardiomyopathy or cardiac arrhythmia (Table S4, Lopes et al. 2013. PubMed ID: 23396983; Table S1, Lopes et al. 2014. PubMed ID: 25351510). This variant is reported in 0.019% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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