ClinVar Miner

Submissions for variant NM_006415.4(SPTLC1):c.399T>G (p.Cys133Trp) (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 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 133 of the SPTLC1 protein (p.Cys133Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in many individuals and families affected 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). Experimental studies have shown that this missense change reduces enzyme activity (PMID: 14990347, 19132419). In addition, transgenic mice with this variant develop a HSAN1 phenotype (PMID:16210380,19923297). This variant disrupts the p.Cys133 amino acid residue in SPTLC1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 11242106, 11242114, 15546589), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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 pathologic Neuropathy, hereditary sensory and autonomic, type 1A 2013-03-07 no assertion criteria provided curation Converted during submission to Pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001004021 SCV001162082 pathogenic Sensorimotor neuropathy no assertion criteria provided research

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