Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255228 | SCV000322089 | likely pathogenic | not provided | 2016-06-14 | criteria provided, single submitter | clinical testing | This variant is denoted PALB2 c.1424C>G at the cDNA level and p.Ser475Ter (S475X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic. |
Invitae | RCV001066196 | SCV001231200 | pathogenic | Familial cancer of breast | 2020-02-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 265326). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser475*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002392782 | SCV002698658 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-10-18 | criteria provided, single submitter | clinical testing | The p.S475* pathogenic mutation (also known as c.1424C>G), located in coding exon 4 of the PALB2 gene, results from a C to G substitution at nucleotide position 1424. This changes the amino acid from a serine to a stop codon within coding exon 4. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Myriad Genetics, |
RCV001066196 | SCV004189434 | pathogenic | Familial cancer of breast | 2023-09-08 | 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. |