Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166878 | SCV000217694 | likely benign | Hereditary cancer-predisposing syndrome | 2024-02-06 | 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. |
Labcorp Genetics |
RCV000474811 | SCV000546910 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 831 of the ATM protein (p.Asp831Gly). This variant is present in population databases (rs587781352, gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 187178). 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. 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 |
RCV000478109 | SCV000570144 | uncertain significance | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28135145, 35893033) |
Color Diagnostics, |
RCV000166878 | SCV000904594 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-10 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 831 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. In a large international case-control study, this variant was reported in 3/60466 breast cancer cases and 1/53461 controls (PMID: 33471991). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). This variant has been identified in 1/251388 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 | RCV000474811 | SCV001138474 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002498828 | SCV002814026 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2021-07-28 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV003315416 | SCV004015194 | uncertain significance | Familial cancer of breast | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glycine at codon 831 of the ATM protein (p.Asp831Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs587781352, ExAC <0.01%). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 187178). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Baylor Genetics | RCV003315416 | SCV004207761 | uncertain significance | Familial cancer of breast | 2024-03-21 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000474811 | SCV002077874 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-09-24 | no assertion criteria provided | clinical testing |