Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV000851935 | SCV000899319 | likely pathogenic | Macrothrombocytopenia | 2019-02-01 | criteria provided, single submitter | research | |
ISTH- |
RCV002222628 | SCV002500849 | likely pathogenic | Platelet-type bleeding disorder 15 | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV002533973 | SCV003197374 | uncertain significance | not provided | 2023-07-12 | criteria provided, single submitter | clinical testing | 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. 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 ACTN1 protein function. ClinVar contains an entry for this variant (Variation ID: 627175). This missense change has been observed in individual(s) with platelet disorders (PMID: 31064749, 34355501). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 653 of the ACTN1 protein (p.Ile653Met). |