ClinVar Miner

Submissions for variant NM_006415.4(SPTLC1):c.399T>G (p.Cys133Trp)

dbSNP: rs119482082
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Total submissions: 5
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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, London Health Sciences Centre 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
GeneReviews RCV001249798 SCV000058073 not provided Neuropathy, hereditary sensory and autonomic, type 1A no assertion provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV001004021 SCV001162082 pathogenic Sensorimotor neuropathy no assertion criteria provided research

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