Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164527 | SCV000215181 | likely benign | Hereditary cancer-predisposing syndrome | 2024-02-28 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589044 | SCV000694185 | uncertain significance | not provided | 2017-07-06 | criteria provided, single submitter | clinical testing | Variant summary: The ATM c.1483A>G (p.Ile495Val) variant causes a missense change involving the alteration of a conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). The variant of interest has not been found in a large, broad control population, ExAC in 121308 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS). |
| Labcorp Genetics |
RCV000627916 | SCV000748800 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 495 of the ATM protein (p.Ile495Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 185158). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
| Color Diagnostics, |
RCV000164527 | SCV002051871 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 495 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). Splice site prediction tools suggest that this variant may impact RNA splicing. To our knowledge, RNA functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer in the literature (PMID: 30287823). This variant has not been identified 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. |
| Mendelics | RCV002247566 | SCV002516939 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing |