Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001179895 | SCV001344696 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001030422 | SCV001410762 | uncertain significance | Familial cancer of breast | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1168 of the PALB2 protein (p.Asp1168Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 830209). 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. |
Ambry Genetics | RCV001179895 | SCV002615995 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-29 | criteria provided, single submitter | clinical testing | The p.D1168E variant (also known as c.3504C>G), located in coding exon 13 of the PALB2 gene, results from a C to G substitution at nucleotide position 3504. The aspartic acid at codon 1168 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration, called a variant of unknown significance, was detected in a female breast cancer patient who was diagnosed at age 44 from a cohort of 2158 individuals who were referred for hereditary cancer genetic testing (Tung N et al. Cancer, 2015 Jan;121:25-33). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Leiden Open Variation Database | RCV001030422 | SCV001193422 | likely benign | Familial cancer of breast | 2019-05-13 | no assertion criteria provided | curation | Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz. |