Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000360950 | SCV000478353 | uncertain significance | Upshaw-Schulman syndrome | 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, this variant 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 (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Gene |
RCV000658135 | SCV000779906 | uncertain significance | not provided | 2018-05-24 | criteria provided, single submitter | clinical testing | The G1276R variant in the ADAMTS13 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G1276R variant is observed in 59/22,158 (0.3%) alleles from individuals of African background in large population cohorts, and no individuals were reported to be homozygous (Lek et al., 2016). The G1276R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret G1276R as a variant of uncertain significance. |
Labcorp Genetics |
RCV000658135 | SCV002229370 | likely benign | not provided | 2024-11-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689727 | SCV005186074 | uncertain significance | not specified | 2024-05-02 | criteria provided, single submitter | clinical testing | Variant summary: ADAMTS13 c.3826G>A (p.Gly1276Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 229922 control chromosomes. To our knowledge, no occurrence of c.3826G>A in individuals affected with Thrombotic Thrombocytopenic Purpura and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 365567). Based on the evidence outlined above, the variant was classified as uncertain significance. |