Submissions for variant NM_013266.4(CTNNA3):c.1128+2T>C

dbSNP: rs1564675010

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001069700	SCV001234888	uncertain significance	Arrhythmogenic right ventricular dysplasia 13	2022-08-09	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 862873). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with CTNNA3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 8 of the CTNNA3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CTNNA3 cause disease.
PreventionGenetics, part of Exact Sciences	RCV003938433	SCV004748586	uncertain significance	CTNNA3-related disorder	2023-11-21	no assertion criteria provided	clinical testing	The CTNNA3 c.1128+2T>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or 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.