ClinVar Miner

Submissions for variant NM_006415.4(SPTLC1):c.1402G>T (p.Ala468Ser) (rs748723735)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000437435 SCV000531301 likely benign not specified 2016-10-25 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488106 SCV000575582 uncertain significance not provided 2016-09-01 criteria provided, single submitter clinical testing
Invitae RCV000692000 SCV000819805 uncertain significance Hereditary sensory and autonomic neuropathy type 1 2020-10-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 468 of the SPTLC1 protein (p.Ala468Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs748723735, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with SPTLC1-related disease. ClinVar contains an entry for this variant (Variation ID: 388906). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001174084 SCV001337204 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.