ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1303T>C (p.Leu435=)

gnomAD frequency: 0.00001  dbSNP: rs748469311
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165265 SCV000215981 likely benign Hereditary cancer-predisposing syndrome 2014-07-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV000252163 SCV000301651 likely benign not specified criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000470029 SCV000558436 likely benign Ataxia-telangiectasia syndrome 2024-01-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000165265 SCV000681965 likely benign Hereditary cancer-predisposing syndrome 2016-06-20 criteria provided, single submitter clinical testing
GeneDx RCV001675648 SCV001894373 benign not provided 2015-05-06 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000165265 SCV002530265 likely benign Hereditary cancer-predisposing syndrome 2021-10-11 criteria provided, single submitter curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003316039 SCV004017369 likely benign Familial cancer of breast 2023-07-07 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003316039 SCV005084521 benign Familial cancer of breast 2024-04-26 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355218 SCV001550038 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Leu435L= variant was not identified in the literature nor was it identified in the LOVD 3.0 databases. The variant was identified in dbSNP (rs748469311) as “with likely benign allele” and ClinVar (interpreted as "likely benign" Invitae and 3 others). The variant was identified in control databases in 8 of 245856 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 2 of 5476 chromosomes (freq: 0.0004), European in 4 of 111,514 chromosomes (freq: 0.00004), and South Asian in 2 of 30778 chromosomes (freq: 0.00007). The variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian and Finnish populations. The p.Leu435= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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.