Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022328 | SCV001184047 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-15 | criteria provided, single submitter | clinical testing | The p.L1448* pathogenic mutation (also known as c.4343T>G), located in coding exon 28 of the ATM gene, results from a T to G substitution at nucleotide position 4343. This changes the amino acid from a leucine to a stop codon within coding exon 28. 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. |
Gene |
RCV002272388 | SCV002558349 | likely pathogenic | not provided | 2022-01-27 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal history of breast cancer in published literature (Akcay 2020) and not observed in controls; This variant is associated with the following publications: (PMID: 31345636, 32658311) |
Invitae | RCV002551851 | SCV003277438 | pathogenic | Ataxia-telangiectasia syndrome | 2022-09-14 | 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: 824810). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 32658311). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1448*) 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). |