Submissions for variant NM_000051.4(ATM):c.5858C>A (p.Thr1953Lys)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002301993	SCV002597858	uncertain significance	Ataxia-telangiectasia syndrome	2023-08-20	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. This variant disrupts the p.Thr1953 amino acid residue in ATM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18634022, 25186627, 26896183, 31214711). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 1953 of the ATM protein (p.Thr1953Lys). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1719233). This variant has not been reported in the literature in individuals affected with ATM-related conditions.