Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129390 | SCV000184156 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-10 | criteria provided, single submitter | clinical testing | The p.W904* pathogenic mutation (also known as c.2712G>A), located in coding exon 7 of the PALB2 gene, results from a G to A substitution at nucleotide position 2712. This changes the amino acid from a tryptophan to a stop codon within coding exon 7. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Gene |
RCV000485246 | SCV000567607 | pathogenic | not provided | 2023-01-30 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals undergoing multi-gene panel testing in published literature (LaDuca et al., 2017); This variant is associated with the following publications: (PMID: 31602316, 28152038) |
| Invitae | RCV000799015 | SCV000938662 | pathogenic | Familial cancer of breast | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp904*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). 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: 141053). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV000129390 | SCV001348380 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 7 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Myriad Genetics, |
RCV000799015 | SCV004188506 | pathogenic | Familial cancer of breast | 2023-09-13 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Baylor Genetics | RCV000799015 | SCV004202787 | likely pathogenic | Familial cancer of breast | 2021-04-28 | criteria provided, single submitter | clinical testing |