ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3693_3695del (p.Leu1231_Ser1232delinsPhe) (rs786203389)

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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 RCV000166672 SCV000217479 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-18 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000233674 SCV000282940 uncertain significance Ataxia-telangiectasia syndrome 2019-12-27 criteria provided, single submitter clinical testing This variant, c.3693_3695delATC, results in the deletion of 2 amino acids and insertion of 1 new amino acid of the ATM protein (p.Leu1231_Ser1232delinsPhe), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 186997). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted and inserted amino acids is currently unknown. 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.
GeneDx RCV000486858 SCV000567616 uncertain significance not provided 2017-08-15 criteria provided, single submitter clinical testing This deletion of three nucleotides in ATM is denoted c.3693_3695delATC at the cDNA level and p.Leu1231_Ser1232delinsPhe (L1231_S1232delinsF) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACTT[delATC]TTCT. This in frame deletion results in the replacement of adjacent Leucine and Serine residues with a single Phenylalanine residue. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Leu1231_Ser1232delinsPhe was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). While the Leucine residue occurs at a position where amino acids with properties similar to Leucine are tolerated across species, the Serine residue is not conserved across species. This variant occurs within the beta-adaptin interaction domain (Tavtigian 2009). Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider ATM Leu1231_Ser1232delinsPhe to be a variant of uncertain significance.
Color RCV000166672 SCV000687494 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-24 criteria provided, single submitter clinical testing
Mendelics RCV000233674 SCV000838525 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing

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