ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.37C>T (p.Arg13Cys) (rs141586345)

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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 RCV000165494 SCV000216225 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000165494 SCV000911423 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-01 criteria provided, single submitter clinical testing
Counsyl RCV000230359 SCV000792114 uncertain significance Ataxia-telangiectasia syndrome 2017-06-08 criteria provided, single submitter clinical testing
GeneDx RCV000589373 SCV000293426 uncertain significance not provided 2018-01-30 criteria provided, single submitter clinical testing This variant is denoted ATM c.37C>T at the cDNA level, p.Arg13Cys (R13C) at the protein level, and results in the change of an Arginine to a Cysteine (CGT>TGT). This variant has been observed in at least two women with breast cancer (Broeks 2000, Broeks 2008, Tavtigian 2009). ATM Arg13Cys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether ATM Arg13Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000589373 SCV000694265 uncertain significance not provided 2015-10-05 criteria provided, single submitter clinical testing
Invitae RCV000230359 SCV000282942 uncertain significance Ataxia-telangiectasia syndrome 2018-09-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 13 of the ATM protein (p.Arg13Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs141586345, ExAC 0.01%). This variant has been reported in the literature in individuals with breast cancer (PMID: 10677309, 17393301, 19781682). ClinVar contains an entry for this variant (Variation ID: 185977). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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