ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.1639G>A (p.Gly547Ser)

dbSNP: rs1306768272
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000698114 SCV000826757 uncertain significance GNE myopathy; Sialuria 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 578 of the GNE protein (p.Gly578Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GNE-related conditions. 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526016 SCV005039568 uncertain significance not specified 2024-03-11 criteria provided, single submitter clinical testing Variant summary: GNE c.1732G>A (p.Gly578Ser) 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 251470 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1732G>A in individuals affected with Inclusion Body Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 575796). Based on the evidence outlined above, the variant was classified as uncertain significance.
Human Genetics Section, Sidra Medicine RCV004686605 SCV005077823 uncertain significance Isolated hereditary giant platelet disorder 2024-07-11 criteria provided, single submitter research Clarification (August 6, 2024): Franklin and VarSome were utilized as supplementary tools to predict the pathogenicity of the identified variant. The patient exhibited developmental dysplasia of the left hip and an increased number of megakaryocytes in the bone biopsy. Consequently, Whole Genome Sequencing (WGS) was performed, which identified the variant responsible for the observed phenotypes. We are currently preparing the publication detailing these findings, and the PubMed ID (PMID) will be provided upon its release.
Natera, Inc. RCV001825370 SCV002075637 uncertain significance GNE myopathy 2021-02-25 no assertion criteria provided clinical testing

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