Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000005070 | SCV000935349 | pathogenic | Hereditary sensory and autonomic neuropathy type 1 | 2023-02-22 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 133 of the SPTLC1 protein (p.Cys133Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary sensory and autonomic neuropathy type 1 (HSAN1) (PMID: 11242106, 11242114, 16364956, 18018475, 22302274, 26681808). ClinVar contains an entry for this variant (Variation ID: 4803). 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 SPTLC1 protein function. Experimental studies have shown that this missense change affects SPTLC1 function (PMID: 14990347, 16210380, 19132419, 19923297). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Cys133 amino acid residue in SPTLC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11242106, 11242114, 15546589). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Molecular Genetics Laboratory, |
RCV001174071 | SCV001337191 | pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
OMIM | RCV001249798 | SCV000025246 | pathogenic | Neuropathy, hereditary sensory and autonomic, type 1A | 2010-07-23 | no assertion criteria provided | literature only | |
Gene |
RCV001249798 | SCV000058073 | not provided | Neuropathy, hereditary sensory and autonomic, type 1A | no assertion provided | literature only | ||
NIHR Bioresource Rare Diseases, |
RCV001004021 | SCV001162082 | pathogenic | Sensorimotor neuropathy | no assertion criteria provided | research |