Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115183 | SCV000149092 | pathogenic | not provided | 2014-01-20 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted ATM c.3931C>T at the cDNA level and p.Gln1311Ter (Q1311X) at the protein level. This substitution creates a nonsense variant, changing a Glutamine to a premature stop codon (CAA>TAA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with recessively-inherited Ataxia-telangiectasia (Perreault 2012). We therefore consider this variant to be pathogenic. |
Ambry Genetics | RCV000492834 | SCV000581443 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-09-26 | criteria provided, single submitter | clinical testing | The p.Q1311* pathogenic mutation (also known as c.3931C>T), located in coding exon 25 of the ATM gene, results from a C to T substitution at nucleotide position 3931. This changes the amino acid from a glutamine to a stop codon within coding exon 25. This mutation has been previously identified in a homozygous state in one individual of Cambodian descent with ataxia-telangiectasia (Perreault S et al. Pediatr. Neurol. 2012 May; 46(5):322-4). In addition to the clinical data presented in the literature, 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 |
RCV003500505 | SCV004296151 | pathogenic | Ataxia-telangiectasia syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1311*) 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 present in population databases (rs200976093, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of ATM-related conditions (PMID: 22520355, 30322717). ClinVar contains an entry for this variant (Variation ID: 127378). For these reasons, this variant has been classified as Pathogenic. |