ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.1942C>T (p.Arg648Trp) (rs537049075)

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
Illumina Clinical Services Laboratory,Illumina RCV001095110 SCV000454549 likely benign Charcot-Marie-Tooth disease, type 4C 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000268641 SCV000454550 likely benign Mononeuropathy of the median nerve, mild 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV000360932 SCV001003297 likely benign Charcot-Marie-Tooth disease type 4 2019-12-31 criteria provided, single submitter clinical testing
Diagnostics Lab (ASPIRE), CSIR - Centre for Cellular and Molecular Biology RCV001030761 SCV001190224 uncertain significance Hereditary motor and sensory neuropathy 2019-12-24 criteria provided, single submitter clinical testing The c.1942C>T variant is not present in publicly available database like Exome Variant Server (EVS), however present in 1000 Genomes, Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP at a low minor allele frequency (MAF<0.001), including one homozygote. The variant is present in our in-house exome database in heterozygous state (MAF~0.005). The variant was reported to ClinVar (Accession ID: VCV000351908.2) with conflicting interpretation of pathogenicity (likely benign/uncertain significance). In-silico pathogenicity prediction programslike SIFT, PolyPhen-2, MutationTaster2, CADD etc. predicted this variant as likely deleterious, however functional assay was not done to prove this. Due to lack of enough evidence the variant has been classified as uncertain significance.

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.