Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566562 | SCV000660647 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-28 | criteria provided, single submitter | clinical testing | The p.G335* pathogenic mutation (also known as c.1003G>T), located in coding exon 7 of the ATM gene, results from a G to T substitution at nucleotide position 1003. This changes the amino acid from a glycine to a stop codon within coding exon 7. 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. |
Labcorp Genetics |
RCV000689138 | SCV000816778 | pathogenic | Ataxia-telangiectasia syndrome | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly335*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 479010). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000689138 | SCV001339035 | likely pathogenic | Ataxia-telangiectasia syndrome | 2020-03-10 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.1003G>T (p.Gly335X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1339C>T (p.Arg447X)). The variant was absent in 251174 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1003G>T in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Myriad Genetics, |
RCV004024453 | SCV004933737 | pathogenic | Familial cancer of breast | 2024-01-11 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |