ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4975A>G (p.Ile1659Val)

gnomAD frequency: 0.00001  dbSNP: rs778632065
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568872 SCV000660642 likely benign Hereditary cancer-predisposing syndrome 2017-08-28 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 RCV000812463 SCV000952777 uncertain significance Ataxia-telangiectasia syndrome 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1659 of the ATM protein (p.Ile1659Val). This variant is present in population databases (rs778632065, gnomAD 0.008%). This missense change has been observed in individual(s) with breast cancer (PMID: 19404735). ClinVar contains an entry for this variant (Variation ID: 479007). 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001538998 SCV001756725 uncertain significance not provided 2021-04-26 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29522266, 19404735)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001538998 SCV002010808 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV001764634 SCV002581389 uncertain significance Familial cancer of breast 2022-02-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV001764634 SCV004207037 uncertain significance Familial cancer of breast 2023-10-08 criteria provided, single submitter clinical testing

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