Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019593 | SCV001180973 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | The c.3275T>C (p.L1092P) alteration is located in exon 12 (coding exon 12) of the PALB2 gene. This alteration results from a T to C substitution at nucleotide position 3275, causing the leucine (L) at amino acid position 1092 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001019593 | SCV001354232 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 1092 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 not been reported in individuals affected with PALB2-related disorders in the literature. 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. |
| Invitae | RCV001369048 | SCV001565476 | uncertain significance | Familial cancer of breast | 2023-03-08 | criteria provided, single submitter | clinical testing | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 823385). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1092 of the PALB2 protein (p.Leu1092Pro). |
| Baylor Genetics | RCV001369048 | SCV004202644 | uncertain significance | Familial cancer of breast | 2023-05-08 | criteria provided, single submitter | clinical testing |