ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.647T>C (p.Val216Ala) (rs779694939)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255797 SCV000321741 pathogenic not provided 2015-04-29 criteria provided, single submitter clinical testing The V216A variant in the GNE gene has been reported previously in multiple patients with GNE-related myopathy (Vasconcelos et al., 2002; Chaouch et al., 2014). The V216A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Functional studies have shown that the V216A variant reduces GNE enzyme activity (Sparks et al., 2005). The V216A variant is a conservative amino acid substitution that alters a highly conserved position in the N-terminal epimerase domain of the GNE enzyme (Sparks et al., 2005).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000255797 SCV000339268 likely pathogenic not provided 2016-03-16 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000255797 SCV000613536 pathogenic not provided 2017-01-24 criteria provided, single submitter clinical testing
Invitae RCV000627756 SCV000638336 pathogenic GNE myopathy; Sialuria 2019-10-03 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 247 of the GNE protein (p.Val247Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs779694939, ExAC 0.003%). This variant has been reported in several individuals affected with myopathy (PMID: 12473769, 24695763, 24136589). In one family, this variant was reported to segregate with inclusion body myopathy and was observed on the opposite chromosome (in trans) from a pathogenic variant (PMID: 12473769). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as p.Val216Ala in the literature. ClinVar contains an entry for this variant (Variation ID: 218297). Experimental studies have shown that this missense change reduces the activity of the GNE-encoded protein, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (PMID: 15987957). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000202427 SCV000789772 likely pathogenic GNE myopathy 2017-02-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV000627756 SCV001163613 likely pathogenic GNE myopathy; Sialuria criteria provided, single submitter clinical testing
OMIM RCV000202427 SCV000257487 pathogenic GNE myopathy 2002-12-10 no assertion criteria provided literature only

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