Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000214436 | SCV000279618 | pathogenic | not provided | 2015-12-04 | criteria provided, single submitter | clinical testing | The E462X nonsense variant in the SH3TC2 gene has been reported previously in association with Charcot-Marie-Tooth disease (DiVincenzo et al., 2014). The E462X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. |
| Illumina Laboratory Services, |
RCV000778757 | SCV000915122 | uncertain significance | SH3TC2-related disorder | 2017-09-14 | criteria provided, single submitter | clinical testing | The SH3TC2 c.1384G>T (p.Glu462Ter) variant is a stop-gained variant and has been identified in one individual with suspected symptoms of Charcot-Marie-Tooth, type 4; however, there is no information on zygosity (DiVincenzo et al. 2014). There are no publications to date regarding the p.Glu462Ter variant and mononeuropathy of the median nerve. Control data are unavailable for this variant, which is reported at a frequency of 0.00003 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the limited evidence and the potential impact of stop-gained variants, the p.Glu462Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for SH3TC2-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV001854739 | SCV002172131 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2021-04-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with SH3TC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 234623). This variant is present in population databases (rs749850181, ExAC 0.003%). This sequence change creates a premature translational stop signal (p.Glu462*) in the SH3TC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SH3TC2 are known to be pathogenic (PMID: 20220177, 27068304). |
| Inherited Neuropathy Consortium | RCV000789720 | SCV000929096 | pathogenic | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |