Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166018 | SCV000216777 | likely benign | Hereditary cancer-predisposing syndrome | 2024-01-22 | 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 |
RCV000228629 | SCV000290806 | uncertain significance | Familial cancer of breast | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 418 of the PALB2 protein (p.Asn418Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 35264596, 35451682). ClinVar contains an entry for this variant (Variation ID: 186426). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PALB2 protein function. 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, |
RCV000166018 | SCV000685863 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-01 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 418 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. In a large breast cancer case-control study, this variant was identified in 1/60465 cases and was absent in the control cohort (PMID: 33471991 - Leiden Open Variation Database DB-ID PALB2_011057). 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 | RCV000228629 | SCV001140040 | uncertain significance | Familial cancer of breast | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001775647 | SCV002013130 | uncertain significance | not provided | 2020-11-04 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV000228629 | SCV005053902 | uncertain significance | Familial cancer of breast | 2024-02-05 | criteria provided, single submitter | clinical testing |