ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8189A>C (p.Gln2730Pro)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000800526 SCV000940247 likely pathogenic Ataxia-telangiectasia syndrome 2018-10-04 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 2730 of the ATM protein (p.Gln2730Pro). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with ataxia-telangiectasia (PMID: 16189143). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Experimental studies have shown that this missense change results in impaired kinase activity of the ATM protein, and causes early embryonic lethality in mice (PMID: 19431188, 16189143, 22869595). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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