ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1801C>T (p.Leu601Phe)

dbSNP: rs1131691685
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000696909 SCV000825490 pathogenic Hypertrophic cardiomyopathy 2018-06-12 criteria provided, single submitter clinical testing This variant has been observed to be de novo in an individual affected with obstructive cardiomyopathy (Invitae) and in several independent individuals affected with hypertrophic cardiomyopathy (PMID: 16858239, 27247418). A different missense substitution at this codon (p.Leu601Val ) has been determined to be likely pathogenic (PMID: 12566107). This suggests that the leucine residue is critical for MYH7 protein function and that other missense substitutions at this position may also be pathogenic. This sequence change replaces leucine with phenylalanine at codon 601 of the MYH7 protein (p.Leu601Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). For these reasons, this variant has been classified as Pathogenic.

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