ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.260C>T (p.Ser87Leu) (rs864309504)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522454 SCV000618293 pathogenic not provided 2017-07-10 criteria provided, single submitter clinical testing The S87L variant in the MORC2 gene has been reported previously, using alternate nomenclature S25L, as a de novo variant in individuals with infantile onset Charot-Marie-Tooth disease (Sevilla et al., 2016; Hyun et al., 2016). The S87L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S87L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret S87L as a pathogenic variant.
Invitae RCV000202460 SCV000655836 pathogenic Charcot-Marie-Tooth disease, axonal, type 2z 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 25 of the MORC2 protein (p.Ser25Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in multiple individuals affected with Charcot-Marie-Tooth disease type 2 (CMT2) (PMID: 26497905, 27105897). ClinVar contains an entry for this variant (Variation ID: 218308). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000202460 SCV000257500 pathogenic Charcot-Marie-Tooth disease, axonal, type 2z 2015-10-24 no assertion criteria provided literature only
Genesis Genome Database RCV000857126 SCV000999704 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001255406 SCV001431806 pathogenic Global developmental delay 2019-11-01 no assertion criteria provided clinical testing

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