Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115168 | SCV000149077 | uncertain significance | not provided | 2022-09-16 | 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; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Observed in individuals with prostate cancer (Karlsson et al., 2021); This variant is associated with the following publications: (PMID: 19781682, 26181193, 28779002, 33436325, 31729406) |
Invitae | RCV000465835 | SCV000546989 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 982 of the ATM protein (p.Arg982Cys). This variant is present in population databases (rs587779830, gnomAD 0.007%). This missense change has been observed in individual(s) with prostate cancer or breast cancer (PMID: 33436325, 35264596). ClinVar contains an entry for this variant (Variation ID: 127363). 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. 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. |
Ambry Genetics | RCV000563065 | SCV000660575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-11 | criteria provided, single submitter | clinical testing | The p.R982C variant (also known as c.2944C>T), located in coding exon 19 of the ATM gene, results from a C to T substitution at nucleotide position 2944. The arginine at codon 982 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in at least one subject in a study of 13087 breast cancer cases and 5488 control individuals in the UK (Decker B et al. J Med Genet, 2017 11;54:732-741). 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. |
Color Diagnostics, |
RCV000563065 | SCV000682091 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 982 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with prostate cancer (PMID: 33436325). This variant has been identified in 5/251040 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. |
Mendelics | RCV000465835 | SCV000838515 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000563065 | SCV002535212 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003460802 | SCV004207127 | uncertain significance | Familial cancer of breast | 2023-09-25 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000465835 | SCV002076503 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-10-16 | no assertion criteria provided | clinical testing |