Submissions for variant NM_001130004.2(ACTN1):c.1294G>A (p.Ala432Thr)

dbSNP: rs1454176065

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852008	SCV000899466	uncertain significance	Macrothrombocytopenia	2019-02-01	criteria provided, single submitter	research
PreventionGenetics, part of Exact Sciences	RCV003396340	SCV004112481	uncertain significance	ACTN1-related disorder	2023-02-06	criteria provided, single submitter	clinical testing	The ACTN1 c.1294G>A variant is predicted to result in the amino acid substitution p.Ala432Thr. This variant has been reported in the heterozygous state in an individual in a cohort study of patients with bleeding disorders (Downes et al. 2019. PubMed ID: 31064749. Suppl3_SNV+INDEL). A different missense variant in the same codon (c.1295C>T,p.Ala432Val) has been reported in an individual with thrombocytopenia (Vincenot et al. 2019. PubMed ID: 31237726) suggesting that substitution of amino acid residue p.Ala432 is not tolerated. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245653	SCV002515755	uncertain significance	Platelet-type bleeding disorder 15		no assertion criteria provided	research