Submissions for variant NM_000051.4(ATM):c.4028T>C (p.Ile1343Thr)

gnomAD frequency: 0.00002  dbSNP: rs1309605588

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000687940	SCV000815535	uncertain significance	Ataxia-telangiectasia syndrome	2021-08-27	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine with threonine at codon 1343 of the ATM protein (p.Ile1343Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Baylor Genetics	RCV004568593	SCV005057192	uncertain significance	Familial cancer of breast	2023-11-28	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001724139	SCV001952566	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001724139	SCV001964476	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000687940	SCV002079103	uncertain significance	Ataxia-telangiectasia syndrome	2019-10-28	no assertion criteria provided	clinical testing