Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000222325 | SCV000277450 | likely benign | Hereditary cancer-predisposing syndrome | 2018-02-12 | 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, |
RCV000587287 | SCV000694304 | uncertain significance | not provided | 2017-04-06 | criteria provided, single submitter | clinical testing | Variant summary: The c.5618G>A (p.Cys1873Tyr) in ATM gene is a missense change that involves a non-conserved nucleotide and 2/4 in silico tools predict benign outcome. The variant of interest is located outside of any known functional domain. The variant is absent from the control population dataset of ExAC (0/120620chrs tested), but is identified in 3/30954chrs tested of gnomAD dataset. This variant has not, to our knowledge, been reported in affected individuals via published reports, but is cited as VUS by a reputable database/clinical laboratory. Taking together, the variant was classified as VUS. |
Labcorp Genetics |
RCV000627966 | SCV000748852 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1873 of the ATM protein (p.Cys1873Tyr). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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: 233138). 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 tolerated. 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, |
RCV000222325 | SCV000904871 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-17 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with tyrosine at codon 1873 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 reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/31378 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. |
Baylor Genetics | RCV003469066 | SCV004208163 | uncertain significance | Familial cancer of breast | 2023-11-18 | criteria provided, single submitter | clinical testing |