ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.9102_9103delinsTT (p.Leu3034_Leu3035delinsPhePhe) (rs730881308)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159637 SCV000209626 uncertain significance not provided 2014-03-31 criteria provided, single submitter clinical testing This variant is denoted ATM c.9102_9103delGCinsTT at the cDNA level and p.Leu3034_Leu3035delinsPhePhe (L3034_L3035delinsFF) at the protein level. The normal sequence, with the bases that are deleted and inserted in brackets, is ATTT[delGCinsTT]TCA. The deletion and insertion results in the replacement of two Leucine residues with two Phenylalanine residues, creating two adjacent missense changes: Leu3034Phe and Leu3035Phe. This combined variant has not, to our knowledge, been reported in the literature as pathogenic or benign. Although one missense variant, Leu3035Phe, has been reported in an individual with Ataxia Telangiectasia who also carried a nonsense ATM variant, phase of the variants was not determined through parental testing (Cavalieri 2006). ATM 9102_9103delGCinsTT was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Leucine and Phenylalanine share similar properties, this is considered a conservative amino acid substitution and is unlikely to affect protein integrity. This variant occurs at a position that is well conserved across species and is located in the FATC domain. Based on currently available information, it is unclear whether this variant is pathogenic or benign. We consider it to be a variant of uncertain significance. This variant appears to be mosaic, as the variant allele was present but underrepresented in comparison to the normal allele. This result was confirmed using alternate, non-overlapping primers, making it unlikely that this result is due to preferential amplification of the normal allele. Therefore, this variant is interpreted to be present in some, but not all, cells in this peripheral blood specimen. Neither Sanger nor Next Generation sequencing is a quantitative test; thus, it is not possible to determine more precisely the level of mosaicism in this specimen. Moreover, the level of mosaicism may be different in other tissues. As somatic mosaicism generally results from a post-zygotic event, parents and siblings are not likely at risk to carry this mosaic mutation. Germline mosaicism and transmission to the offspring of this patient, however, cannot be excluded.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.