ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.811C>A (p.Leu271Ile) (rs730881339)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000211953 SCV000209684 uncertain significance not provided 2017-12-06 criteria provided, single submitter clinical testing This variant is denoted ATM c.811C>A at the cDNA level, p.Leu271Ile (L271I) at the protein level, and results in the change of a Leucine to an Isoleucine (CTT>ATT). This variant was observed in at least one individual with breast cancer (Decker 2017). ATM Leu271Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Leucine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. ATM Leu271Ile is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether ATM Leu271Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000159681 SCV000218086 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-01 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)
Invitae RCV000472609 SCV000547162 uncertain significance Ataxia-telangiectasia syndrome 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 271 of the ATM protein (p.Leu271Ile). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs730881339, ExAC 0.002%). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 181916). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color RCV000159681 SCV000682455 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-10 criteria provided, single submitter clinical testing

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