ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4931T>C (p.Met1644Thr) (rs55843558)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563094 SCV000668089 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-15 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000563094 SCV000913950 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-11 criteria provided, single submitter clinical testing
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030595 SCV001193480 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV001174554 SCV001337713 uncertain significance not specified 2020-01-27 criteria provided, single submitter clinical testing Variant summary: ATM c.4931T>C (p.Met1644Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251042 control chromosomes (gnomAD). However, the variant was reported in Japanese healthy controls with an allele frequency of 0.0003 (in jMorp), and 0.0008 (i.e. 2/1201 healthy Japanese individuals; in HGVD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. In a recent case-control association study involving breast cancer patients and controls of Japanese ancestry (Momozawa 2018), the variant was found in 5/7051 female breast cancer patients (while not found in 11241 healthy female controls) and was also identified in 5/12490 healthy male controls (but not found in 0/53 male cases). This report does not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all of them classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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