Submissions for variant NM_000051.4(ATM):c.508G>A (p.Val170Met)

dbSNP: rs786202781

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001176394	SCV001340368	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-04	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 170 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001875811	SCV002266538	uncertain significance	Ataxia-telangiectasia syndrome	2021-07-24	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 918666). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 170 of the ATM protein (p.Val170Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492225	SCV004239305	uncertain significance	Breast and/or ovarian cancer	2023-04-17	criteria provided, single submitter	clinical testing