ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.562C>T (p.Gln188Ter)

dbSNP: rs1456983114
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
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000505958 SCV000605344 likely pathogenic not provided 2017-05-23 criteria provided, single submitter clinical testing The p.Gln188Ter variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. The c.562C>T variant creates a termination codon in the TCN2 protein at codon 188 in exon 4 which is predicted to result in a truncated or absent protein product. This variant is listed in the genome Aggregation Database with an overall population frequency of 0.0004 percent (identified on 1 out of 246,168 chromosomes). Based on these observations, the p.Gln188Ter variant has been classified as pathogenic.
Ambry Genetics RCV000622503 SCV000740822 pathogenic Inborn genetic diseases 2015-02-04 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000779371 SCV000915972 uncertain significance Transcobalamin II deficiency 2018-10-11 criteria provided, single submitter clinical testing The TCN2 c.562C>T (p.Gln188Ter) variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for transcobalamin II deficiency.
Labcorp Genetics (formerly Invitae), Labcorp RCV000779371 SCV003006244 pathogenic Transcobalamin II deficiency 2023-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln188*) in the TCN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCN2 are known to be pathogenic (PMID: 7980584, 20352340). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 440326). For these reasons, this variant has been classified as Pathogenic.

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.