ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2510A>T (p.Lys837Met) (rs1060501439)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467403 SCV000546208 uncertain significance Hypertrophic cardiomyopathy 2016-10-21 criteria provided, single submitter clinical testing This sequence change replaces lysine with methionine at codon 837 of the MYH7 protein (p.Lys837Met). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYH7-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Petrovsky Russian Research Center of Surgery, The Federal Agency for Scientific Organizations RCV000758564 SCV000882695 likely pathogenic Left ventricular hypertrophy; Left ventricular noncompaction cardiomyopathy 2018-12-05 criteria provided, single submitter research The c.2510 A>T (p.K837M) variant was detected in a patient with left ventricular non-compaction, hypertrophy of left ventricular wall and dilatation of cardiac chambers. To our knowledge, p.K837M variant is absent from large population studies; it is present in dbSNP and classified to be of uncertain clinical significance. Online prediction tools (PolyPhen2, SIFT, MutationTaster) all classify the p.K837M variant as a probably pathogenic disease-causing variant. No DNA samples of family members of our patient were available for familial screening. However, p.K837M variant is located within a mutation HCM cluster, described by Walsh (2017). According to Walsh 2017, variants detected in patients with HCM and located within the cluster are highly likely to be pathogenic. We observed hypertrophy of left ventricular wall in our patient. Thus, we consider the p.K837M variant to be likely pathogenic.

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