Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000498431 | SCV000589765 | pathogenic | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 34189813, 28771897, 32693025, 33098801) |
Ambry Genetics | RCV000624267 | SCV000742758 | uncertain significance | Inborn genetic diseases | 2018-01-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000689169 | SCV000816809 | pathogenic | Charcot-Marie-Tooth disease axonal type 2Z | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 394 of the MORC2 protein (p.Tyr394Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of MORC2-related conditions (PMID: 28771897, 32693025). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 432089). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Institute Of Human Genetics Munich, |
RCV000689169 | SCV001149839 | pathogenic | Charcot-Marie-Tooth disease axonal type 2Z | 2018-04-18 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003983095 | SCV004800531 | pathogenic | MORC2-related condition | 2024-02-17 | criteria provided, single submitter | clinical testing | The MORC2 c.1181A>G variant is predicted to result in the amino acid substitution p.Tyr394Cys. This variant was reported in individuals with neurodevelopmental disorders or suspected Charcot-Marie-Tooth disease; in several, this variant arose de novo (see, for example, Guillen Sacoto et al. 2020. PubMed ID: 32693025; Zech et al. 2020. PubMed ID: 33098801, supplementary data, reported as p.Tyr332Cys; Sivera et al. 2021. PubMed ID: 34189813; Frongia et al. 2021. PubMed ID: 34630290). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. |