Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480809 | SCV000570700 | uncertain significance | not provided | 2023-11-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in a blood sample from a patient with chronic lymphocytic leukemia (PMID: 11756185); This variant is associated with the following publications: (PMID: 12400598, 11756185) |
| Ambry Genetics | RCV000570473 | SCV000668142 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-07-25 | criteria provided, single submitter | clinical testing | The p.P434S variant (also known as c.1300C>T), located in coding exon 9 of the ATM gene, results from a C to T substitution at nucleotide position 1300. The proline at codon 434 is replaced by serine, an amino acid with similar properties. One study detected this alteration in 1/50 B-cell chronic lymphocytic leukemia tumors; the germline or somatic origin of this alteration was not determined, and the tumor harboring this alteration showed normal ATM protein expression (Stankovic T et al. Blood, 2002 Jan;99:300-9). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000794458 | SCV000933868 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 434 of the ATM protein (p.Pro434Ser). 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: 421484). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |