ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.1753C>T (p.Arg585Cys)

gnomAD frequency: 0.00002  dbSNP: rs548292999
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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 RCV000688838 SCV000816462 uncertain significance Charcot-Marie-Tooth disease axonal type 2Z 2024-05-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 585 of the MORC2 protein (p.Arg585Cys). This variant is present in population databases (rs548292999, gnomAD 0.01%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis and/or Charcot-Marie-Tooth disease type 2 (CMT2) (PMID: 26659848, 31475037). This variant is also known as p.R523C. ClinVar contains an entry for this variant (Variation ID: 568470). 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 MORC2 protein function. 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.
GeneDx RCV001775959 SCV002012880 uncertain significance not provided 2023-08-28 criteria provided, single submitter clinical testing Previously reported in one family with CMT; however, the variant did not segregate with disease in the family, the presence of the variant was not confirmed, and the authors concluded it was likely not pathogenic (Albulym et al., 2016); Reported as R523C in individual with amyotrophic lateral sclerosis; however no further information was provided (Tripolszki et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28492532, 26659848, 31475037)
Genesis Genome Database RCV000857116 SCV000999694 uncertain significance Neuronopathy, distal hereditary motor, autosomal dominant 2019-08-14 no assertion criteria provided research

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