Submissions for variant NM_001903.5(CTNNA1):c.99del (p.Thr34fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV003455920	SCV004186744	pathogenic	Hereditary diffuse gastric adenocarcinoma	2023-07-05	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003720912	SCV004504272	pathogenic	not provided	2023-03-07	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with CTNNA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr34Hisfs*7) in the CTNNA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTNNA1 are known to be pathogenic (PMID: 32051609, 34425242). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003946638	SCV004758183	uncertain significance	CTNNA1-related disorder	2023-11-07	no assertion criteria provided	clinical testing	The CTNNA1 c.99delT variant is predicted to result in a frameshift and premature protein termination (p.Thr34Hisfs*7). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. Currently, there is not sufficient evidence demonstrating that loss of function variants in CTNNA1 are pathogenic. However, a small number of CTNNA1 loss of function variants have been reported in individuals with gastric and breast cancer (Clark et al. 2020. PMID: 32051609). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.