Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000132535 | SCV000187632 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-30 | criteria provided, single submitter | clinical testing | The p.D1641H variant (also known as c.4921G>C), located in coding exon 32 of the ATM gene, results from a G to C substitution at nucleotide position 4921. The aspartic acid at codon 1641 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000225809 | SCV000282972 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1641 of the ATM protein (p.Asp1641His). This variant is present in population databases (rs587782896, gnomAD 0.002%). 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: 143016). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Gene |
RCV000478375 | SCV000570645 | uncertain significance | not provided | 2023-05-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in an individual with lung cancer (Lu et al., 2015); This variant is associated with the following publications: (PMID: 27060149, 26689913) |
| Color Diagnostics, |
RCV000132535 | SCV000687584 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-17 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with histidine at codon 1641 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with lung adenocarcinoma (PMID: 26689913). This variant has also been identified in 3/282394 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Counsyl | RCV000225809 | SCV000791168 | uncertain significance | Ataxia-telangiectasia syndrome | 2017-05-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003474793 | SCV004204446 | uncertain significance | Familial cancer of breast | 2023-10-23 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000225809 | SCV002075431 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-09-29 | no assertion criteria provided | clinical testing |