Submissions for variant NM_000257.4(MYH7):c.1888C>A (p.Pro630Thr)

dbSNP: rs397516124

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001322988	SCV001513885	uncertain significance	Hypertrophic cardiomyopathy	2021-10-16	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This sequence change replaces proline with threonine at codon 630 of the MYH7 protein (p.Pro630Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. 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).
Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences	RCV003320245	SCV002600910	likely pathogenic	Myosin storage myopathy		no assertion criteria provided	research