Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001015624 | SCV001176474 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-09-17 | criteria provided, single submitter | clinical testing | The p.L822* pathogenic mutation (also known as c.2465T>G), located in coding exon 15 of the ATM gene, results from a T to G substitution at nucleotide position 2465. This mutation has been identified in one Austrian family with hereditary breast and/or ovarian cancer (Thorstenson YR et al. Cancer Res. 2003 Jun;63(12):3325-33). This changes the amino acid from a leucine to a stop codon within coding exon 15. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Invitae | RCV003500625 | SCV004296147 | pathogenic | Ataxia-telangiectasia syndrome | 2023-04-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 821323). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 12810666). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Leu822*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). |