Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001125485 | SCV003916013 | uncertain significance | Glanzmann thrombasthenia | 2023-01-17 | reviewed by expert panel | curation | The variant NM_000212.3:c.1459C>T is a missense variant causing a substitution of arginine for cysteine at amino acid position 487. The highest population minor allele frequency for this variant in gnomAD v 2.1.1 is 0.0001002 (2/19952 alleles) in the East Asian population, which is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting. Additionally, the computational predictor REVEL gives a score of .44, which is above the ClinGen PD VCEP threshold of <0.25 for BP4, but below the ClinGen PD VCEP PP3 threshold of >0.7. The variant was identified in a predispositional screen of a healthy population by Illumina, and has not been associated with any individuals with Glanzmann thrombasthenia thus far in the scientific literature. In summary, this variant meets the criteria to be classified as Uncertain significance - insufficient evidence for autosomal recessive Glanzmann Thrombasthenia based on ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP. |
| Illumina Laboratory Services, |
RCV001125485 | SCV001284559 | uncertain significance | Glanzmann thrombasthenia | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Fulgent Genetics, |
RCV002482242 | SCV002786911 | uncertain significance | Myocardial infarction, susceptibility to; Glanzmann thrombasthenia 2; Bleeding disorder, platelet-type, 24 | 2021-07-10 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002558237 | SCV003239696 | uncertain significance | not provided | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 487 of the ITGB3 protein (p.Arg487Cys). This variant is present in population databases (rs369140365, gnomAD 0.01%). 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: 890713). 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. |
| Revvity Omics, |
RCV002558237 | SCV003813851 | uncertain significance | not provided | 2023-08-08 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003147592 | SCV003835323 | uncertain significance | Bleeding disorder, platelet-type, 24 | 2022-08-18 | criteria provided, single submitter | clinical testing |