Submissions for variant NM_000051.4(ATM):c.1159A>C (p.Lys387Gln)

dbSNP: rs786202686

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165621	SCV000216357	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-27	criteria provided, single submitter	clinical testing	The p.K387Q variant (also known as c.1159A>C), located in coding exon 8 of the ATM gene, results from an A to C substitution at nucleotide position 1159. The lysine at codon 387 is replaced by glutamine, an amino acid with similar properties. This alteration was identified in a homozygous state in an individual with a clinical diagnosis of ataxia telangiectasia (Amirifar P et al. Pediatr Allergy Immunol, 2021 Aug;32:1316-1326). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000693825	SCV000822244	uncertain significance	Ataxia-telangiectasia syndrome	2024-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 387 of the ATM protein (p.Lys387Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of ataxia-telangiectasia (PMID: 33547824). ClinVar contains an entry for this variant (Variation ID: 186092). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATM protein function with a negative predictive value of 95%. Studies have shown that this missense change is associated with inconclusive levels of altered splicing (internal data). 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.
Color Diagnostics, LLC DBA Color Health	RCV000165621	SCV001344535	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000693825	SCV001737348	uncertain significance	Ataxia-telangiectasia syndrome	2021-06-10	criteria provided, single submitter	clinical testing