ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2189G>A (p.Cys730Tyr) (rs587781595)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129658 SCV000184456 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-30 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000167916 SCV000218564 uncertain significance Ataxia-telangiectasia syndrome 2019-12-21 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 730 of the ATM protein (p.Cys730Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs587781595, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 141238). 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: "Deleterious"; PolyPhen-2: "Possibly 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.
Fulgent Genetics,Fulgent Genetics RCV000515399 SCV000611349 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2017-05-23 criteria provided, single submitter clinical testing
Color RCV000129658 SCV000682038 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000167916 SCV001260417 uncertain significance Ataxia-telangiectasia syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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