Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002514182 | SCV003278344 | pathogenic | not provided | 2022-11-22 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs587776986, gnomAD 0.1%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 417 of the SBF1 protein (p.Met417Val). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 23749797). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. 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 not expected to disrupt SBF1 protein function. ClinVar contains an entry for this variant (Variation ID: 51005). |
OMIM | RCV000043693 | SCV000071706 | pathogenic | Charcot-Marie-Tooth disease type 4B3 | 2013-07-09 | no assertion criteria provided | literature only | |
Department of Pediatrics, |
RCV001252745 | SCV001163888 | uncertain significance | Microcephaly | no assertion criteria provided | research |