ClinVar Miner

Submissions for variant NM_007289.4(MME):c.1735G>A (p.Gly579Ser)

gnomAD frequency: 0.00001  dbSNP: rs767928746
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198856 SCV001369851 uncertain significance Spinocerebellar ataxia 43 2020-03-31 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PP3.
GeneDx RCV001797160 SCV002038848 uncertain significance not provided 2021-06-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Labcorp Genetics (formerly Invitae), Labcorp RCV001797160 SCV002251264 uncertain significance not provided 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 579 of the MME protein (p.Gly579Ser). This variant is present in population databases (rs767928746, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MME-related conditions. ClinVar contains an entry for this variant (Variation ID: 931880). 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) performed at Invitae indicates that this missense variant is expected to disrupt MME protein function with a positive predictive value of 80%. 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.
GenomeConnect, ClinGen RCV001824932 SCV002075250 not provided Charcot-Marie-Tooth disease type 2; Charcot-Marie-Tooth disease axonal type 2T; MME-related autosomal dominant Charcot Marie Tooth disease type 2 no assertion provided phenotyping only Variant classified as Uncertain significance and reported on 07-21-2021 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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