Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
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, |
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 |
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. |