ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5156A>G (p.Asn1719Ser) (rs183531638)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485988 SCV000570484 uncertain significance not provided 2017-12-05 criteria provided, single submitter clinical testing This variant is denoted ATM c.5156A>G at the cDNA level, p.Asn1719Ser (N1719S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in a glioblastoma (Xiu 2016). ATM Asn1719Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Asparagine and Serine share similar properties, this is considered a conservative amino acid substitution. ATM Asn1719Ser 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 Asn1719Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000546123 SCV000622568 uncertain significance Ataxia-telangiectasia syndrome 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1719 of the ATM protein (p.Asn1719Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs183531638, ExAC 0.009%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 421320). 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.
Ambry Genetics RCV000565111 SCV000660601 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-20 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000565111 SCV000682252 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-07 criteria provided, single submitter clinical testing

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