Submissions for variant NM_000051.4(ATM):c.8113G>T (p.Val2705Leu)

dbSNP: rs587779870

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212078	SCV000149170	uncertain significance	not provided	2014-01-10	criteria provided, single submitter	clinical testing	This variant is denoted ATM c.8113G>T at the cDNA level, p.Val2705Leu (V2705L) at the protein level, and results in the change of a Valine to a Leucine (GTA>TTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val2705Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one neutral non-polar amino acid for another, altering a position that is highly variable throughout evolution and is not located in a known functional domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether ATM Val2705Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000115261	SCV000184526	likely benign	Hereditary cancer-predisposing syndrome	2024-01-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000464258	SCV000546757	uncertain significance	Ataxia-telangiectasia syndrome	2023-03-11	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs587779870, gnomAD 0.0009%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 127455). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2705 of the ATM protein (p.Val2705Leu).
Color Diagnostics, LLC DBA Color Health	RCV000115261	SCV001353447	uncertain significance	Hereditary cancer-predisposing syndrome	2019-06-05	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000115261	SCV002537900	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-25	criteria provided, single submitter	curation
Baylor Genetics	RCV004566997	SCV005056989	uncertain significance	Familial cancer of breast	2024-02-14	criteria provided, single submitter	clinical testing