Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160844 | SCV000211520 | uncertain significance | not provided | 2022-11-25 | criteria provided, single submitter | clinical testing | Not observed at 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: 24485656, 19609323, 20871615, 26489409) |
| Ambry Genetics | RCV000216145 | SCV000276693 | likely benign | Hereditary cancer-predisposing syndrome | 2024-03-21 | 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 |
RCV000555792 | SCV000633366 | uncertain significance | Familial cancer of breast | 2024-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 900 of the PALB2 protein (p.Ala900Val). This variant is present in population databases (rs730881890, gnomAD 0.006%). This missense change has been observed in individual(s) with breast cancer (PMID: 26489409). ClinVar contains an entry for this variant (Variation ID: 182769). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PALB2 protein function with a negative predictive value of 80%. 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, |
RCV000216145 | SCV000911946 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-21 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 900 of the PALB2 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 been detected in an individual affected with breast cancer (PMID: 26489409). This variant has been identified in 1/251492 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. |
| Fulgent Genetics, |
RCV002485001 | SCV002792192 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 | 2021-07-21 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000555792 | SCV005053911 | uncertain significance | Familial cancer of breast | 2024-01-26 | criteria provided, single submitter | clinical testing |