ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.3818A>G (p.Asn1273Ser)

dbSNP: rs1383779893
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000549085 SCV000648253 uncertain significance Hypertrophic cardiomyopathy 14 2020-09-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1273 of the MYH6 protein (p.Asn1273Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYH6-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function and splicing. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004984969 SCV005451638 uncertain significance Cardiovascular phenotype 2024-07-01 criteria provided, single submitter clinical testing The p.N1273S variant (also known as c.3818A>G), located in coding exon 25 of the MYH6 gene, results from an A to G substitution at nucleotide position 3818. The asparagine at codon 1273 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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