ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.1994C>G (p.Ser665Cys)

gnomAD frequency: 0.00001  dbSNP: rs1402143255
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001924018 SCV002205475 uncertain significance Charcot-Marie-Tooth disease axonal type 2Z 2022-10-17 criteria provided, single submitter clinical testing 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. 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 MORC2 protein function. ClinVar contains an entry for this variant (Variation ID: 1424761). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 665 of the MORC2 protein (p.Ser665Cys).
Baylor Genetics RCV001924018 SCV003835043 uncertain significance Charcot-Marie-Tooth disease axonal type 2Z 2021-05-07 criteria provided, single submitter clinical testing
Laboratory of Functional Genomics, Research Centre for Medical Genetics RCV001924018 SCV005626400 uncertain significance Charcot-Marie-Tooth disease axonal type 2Z criteria provided, single submitter clinical testing Variant c.1994C>G in MORC2 was found in a Patient with clinical signs of Charcot–Marie–Tooth disease. Segregation analysis was not performed. This variant is found in gnomAD with frequency 0.00000248. For functional characterization of the variant a vector, expressing MORC2 fused with Flag tag at C-terminal end, was created. Transfection of the plasmid into HEK293T cells followed by Western blotting revealed slight reduction of MORC2 protein quantity compared to wt vector. In summary, c.1994C>G variant meets criteria to be classified as variant of unknown significance.

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