Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000561696 | SCV000670636 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-13 | criteria provided, single submitter | clinical testing | The p.E878* pathogenic mutation (also known as c.2632G>T), located in coding exon 7 of the PALB2 gene, results from a G to T substitution at nucleotide position 2632. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. This mutation has been detected in an individual with ovarian cancer (Koczkowska et al. Cancers (Basel) 2018 Nov;10(11). In addition to the clinical data presented in the literature, 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. |
Invitae | RCV000635833 | SCV000757258 | pathogenic | Familial cancer of breast | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu878*) 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: 484176). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV000635833 | SCV004188547 | 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. |
Leiden Open Variation Database | RCV001030334 | SCV001193268 | pathogenic | not provided | 2019-05-13 | no assertion criteria provided | curation | Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Gemeinschaftspraxis f??r Humangenetik Dresden. |