Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000363147 | SCV000403746 | uncertain significance | Glanzmann thrombasthenia | 2018-01-13 | 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. |
| Labcorp Genetics |
RCV002521113 | SCV003233224 | uncertain significance | not provided | 2022-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 711 of the ITGB3 protein (p.Pro711Ser). This variant is present in population databases (rs138729147, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ITGB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 323872). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ITGB3 protein function. 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. |
| Breakthrough Genomics, |
RCV002521113 | SCV005192940 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004701411 | SCV005203892 | uncertain significance | not specified | 2024-07-02 | criteria provided, single submitter | clinical testing | Variant summary: ITGB3 c.2131C>T (p.Pro711Ser) results in a non-conservative amino acid change located in the Integrin beta subunit, tail (IPR012896) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 1614142 control chromosomes, predominantly at a frequency of 0.0013 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes, suggesting the variant could be benign. c.2131C>T has been reported in the literature in at least one individual affected with mild isolated nonsyndromic thrombocytopenia without reported second variant (e.g. Gueguen_2020). This report does not provide unequivocal conclusions about association of the variant with Glanzmann Thrombasthenia 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 32757236). ClinVar contains an entry for this variant (Variation ID: 323872). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |