ClinVar Miner

Submissions for variant NM_001256545.2(MEGF10):c.2320T>C (p.Cys774Arg)

gnomAD frequency: 0.00002  dbSNP: rs387907072
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000023955 SCV001581111 pathogenic MEGF10-related myopathy 2025-02-03 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 774 of the MEGF10 protein (p.Cys774Arg). This variant is present in population databases (rs387907072, gnomAD 0.005%). This missense change has been observed in individuals with congenital myopathy (PMID: 22101682, 22371254). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30965). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MEGF10 function (PMID: 23954233, 28498977). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV003156219 SCV002022782 likely pathogenic not provided 2019-07-18 criteria provided, single submitter clinical testing
GeneDx RCV003156219 SCV003845915 likely pathogenic not provided 2022-09-29 criteria provided, single submitter clinical testing Published functional studies suggest a damaging effect with impaired proliferation and migration of myoblasts (Saha et al., 2017); 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: 34740639, 34328698, 23954233, 22101682, 34828389, Chahin_2015_Abstract, 27460346, 27170117, 31267131, 22371254, 28498977)
OMIM RCV000023955 SCV000045246 pathogenic MEGF10-related myopathy 2012-05-01 no assertion criteria provided literature only
OMIM RCV000023956 SCV003841128 pathogenic Congenital myopathy 10b, mild variant 2012-05-01 no assertion criteria provided literature only

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