ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2099A>G (p.Glu700Gly)

dbSNP: rs1892684240
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001317562 SCV001508231 uncertain significance Hypertrophic cardiomyopathy 2020-08-14 criteria provided, single submitter clinical testing 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 missense change is located in a region of the MYH7 protein where a significant number of previously reported MYH7 missense mutations are found (PMID: 27532257). These observations suggest that this may be a clinically significant region of the protein. 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 and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of MYH7-related conditions (PMID: 26025024, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 700 of the MYH7 protein (p.Glu700Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine.
Illumina Laboratory Services, Illumina RCV004528461 SCV002038523 likely pathogenic MYH7-related disorder 2021-05-12 criteria provided, single submitter clinical testing The MYH7 c.2099A>G (p.Glu700Gly) variant is a missense variant that has been reported in a heterozygous state in four individuals from a family presenting with left ventricular noncompaction cardiomyopathy (Bainbridge et al. 2015). This variant was reported to segregate with disease in this family, and was absent in three unaffected family members. It is located in a region of exon 19 where several nearby MYH7 missense variants have been reported in relation to cardiac phenotypes (Walsh et al. 2017). The p.Glu700Gly variant is not found in the Genome Aggregation Database (version 2.1.1 or version 3.1.2) in a region of good sequence coverage, so the variant is presumed to be rare. Based on the evidence the p.Glu700Gly variant is classified as likely pathogenic for MYH7-related disorders.
GeneDx RCV004794527 SCV005414749 uncertain significance not provided 2024-05-23 criteria provided, single submitter clinical testing Reported in a family with multiple individuals affected with LVNC (PMID: 26025024); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 29300372, 26025024)

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