Submissions for variant NM_000051.4(ATM):c.7858G>C (p.Val2620Leu)

dbSNP: rs1427723678

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001026878	SCV001189348	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-28	criteria provided, single submitter	clinical testing	The p.V2620L variant (also known as c.7858G>C), located in coding exon 52 of the ATM gene, results from a G to C substitution at nucleotide position 7858. The valine at codon 2620 is replaced by leucine, an amino acid with highly similar properties. 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	RCV001042524	SCV001206207	uncertain significance	Ataxia-telangiectasia syndrome	2023-08-08	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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 827290). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2620 of the ATM protein (p.Val2620Leu).
Color Diagnostics, LLC DBA Color Health	RCV001026878	SCV001349144	uncertain significance	Hereditary cancer-predisposing syndrome	2020-10-13	criteria provided, single submitter	clinical testing	This missense variant replaces valine with leucine at codon 2620 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 hereditary cancer 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.
Baylor Genetics	RCV003467692	SCV004210160	uncertain significance	Familial cancer of breast	2023-07-14	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492211	SCV004239505	uncertain significance	Breast and/or ovarian cancer	2023-06-01	criteria provided, single submitter	clinical testing