ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.736C>T (p.Arg246Trp) (rs773729410)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178150 SCV000230155 pathogenic not provided 2016-05-19 criteria provided, single submitter clinical testing
Invitae RCV000700059 SCV000828798 pathogenic GNE myopathy; Sialuria 2017-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 277 of the GNE protein (p.Arg277Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs773729410, ExAC 0.003%). This variant has been reported as compound heterozygous with another rare GNE variant in more than four individuals with hereditary inclusion body myopathy (PMID: 15987957, 22507750, 21307865, 24136589, 12409274). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with hereditary inclusion body myopathy (PMID: 26231298). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 197184). Experimental studies have shown that this missense change results in significantly reduced epimerase activity of the GNE protein (PMID: 15987957). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000984181 SCV001132210 likely pathogenic GNE myopathy 2018-09-26 no assertion criteria provided clinical testing

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