ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5488A>G (p.Met1830Val) (rs587781622)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129712 SCV000184515 likely benign Hereditary cancer-predisposing syndrome 2018-11-23 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign)
Invitae RCV000199250 SCV000254121 likely benign Ataxia-telangiectasia syndrome 2019-12-17 criteria provided, single submitter clinical testing
GeneDx RCV000590655 SCV000292471 uncertain significance not provided 2018-07-11 criteria provided, single submitter clinical testing This variant is denoted ATM c.5488A>G at the cDNA level, p.Met1830Val (M1830V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant was observed in at least one individual with a personal history of breast cancer (Yehia 2018). ATM Met1830Val 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 that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Met1830Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000590655 SCV000694303 uncertain significance not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The ATM c.5488A>G (p.Met1830Val) variant involves the alteration of a non-conserved nucleotide and 4/4 in silico tools (SNPsandGo not captured here due to low reliability index) predict a benign outcome. This variant was found in 2/121150 control chromosomes at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005). Multiple publications have cited the variant as an assumed somatic occurrence, however, information is limited. In addition, multiple clinical diagnostic laboratories classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Color RCV000129712 SCV000910899 likely benign Hereditary cancer-predisposing syndrome 2016-01-04 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000590655 SCV001143114 uncertain significance not provided 2019-05-17 criteria provided, single submitter clinical testing
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030597 SCV001193482 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research

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