Submissions for variant NM_000257.4(MYH7):c.625C>A (p.Gln209Lys)

dbSNP: rs878853840

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000234529	SCV000284291	uncertain significance	Hypertrophic cardiomyopathy	2021-09-02	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine with lysine at codon 209 of the MYH7 protein (p.Gln209Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 29540472; Invitae). ClinVar contains an entry for this variant (Variation ID: 237442). 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 tolerated. 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). 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	RCV002365176	SCV002660793	uncertain significance	Cardiovascular phenotype	2020-02-24	criteria provided, single submitter	clinical testing	The p.Q209K variant (also known as c.625C>A), located in coding exon 5 of the MYH7 gene, results from a C to A substitution at nucleotide position 625. The glutamine at codon 209 is replaced by lysine, an amino acid with similar properties, and is located in the head domain. This variant was reported in an individual from a dilated cardiomyopathy cohort in whom it may have co-occurred with a second MYH7 variant (Hazebroek MR et al. Circ Heart Fail, 2018 03;11:e004682). A different variant affecting this codon (p.Q209E, c.625C>G) was detected in a hypertrophic cardiomyopathy cohort (Santos S et al. BMC Med. Genet., 2012 Mar;13:17). This amino acid position is well conserved in available vertebrate species; however, lysine is the reference amino acid in other 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.
Baylor Genetics	RCV003147421	SCV003834816	uncertain significance	Hypertrophic cardiomyopathy 1	2022-12-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003147417	SCV003835784	uncertain significance	Dilated cardiomyopathy 1S	2022-12-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003147422	SCV003835878	uncertain significance	Myopathy, myosin storage, autosomal recessive	2022-12-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003147420	SCV003836050	uncertain significance	MYH7-related skeletal myopathy	2022-12-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003320141	SCV003836051	uncertain significance	Myosin storage myopathy	2022-12-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003320141	SCV003836061	uncertain significance	Myosin storage myopathy	2022-12-05	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723816	SCV001954683	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001723816	SCV001969990	uncertain significance	not provided		no assertion criteria provided	clinical testing