ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.1807C>T (p.Leu603Phe)

gnomAD frequency: 0.00001  dbSNP: rs372732220
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000296082 SCV000335207 uncertain significance not provided 2015-09-15 criteria provided, single submitter clinical testing
Counsyl RCV000664508 SCV000788480 uncertain significance GNE myopathy 2017-12-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001247004 SCV001420401 pathogenic GNE myopathy; Sialuria 2023-05-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GNE protein function. ClinVar contains an entry for this variant (Variation ID: 283229). This missense change has been observed in individual(s) with GNE-related myopathy (PMID: 22507750, 24027297, 32505938). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs372732220, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 634 of the GNE protein (p.Leu634Phe).
Revvity Omics, Revvity RCV000296082 SCV003815068 uncertain significance not provided 2022-06-24 criteria provided, single submitter clinical testing
Baylor Genetics RCV000664508 SCV004199380 likely pathogenic GNE myopathy 2024-03-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004586657 SCV005077244 uncertain significance not specified 2024-04-18 criteria provided, single submitter clinical testing Variant summary: GNE c.1900C>T (p.Leu634Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251450 control chromosomes (gnomAD). c.1900C>T has been reported in the literature in individuals affected with Inclusion Body Myopathy 2 (Mori-Yoshimura_2012, Cho_2014, Paul_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 22507750, 24027297, 32505938). ClinVar contains an entry for this variant (Variation ID: 283229). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Natera, Inc. RCV000664508 SCV002075629 uncertain significance GNE myopathy 2021-06-22 no assertion criteria provided clinical testing

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