Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000217992 | SCV000277432 | pathogenic | Hereditary cancer-predisposing syndrome | 2015-07-21 | criteria provided, single submitter | clinical testing | The p.E892* pathogenic mutation (also known as c.2674G>T) located in coding exon 7 of the PALB2 gene, results from a G to T substitution at nucleotide position 2674. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Invitae | RCV001045962 | SCV001209839 | pathogenic | Familial cancer of breast | 2023-06-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 233122). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28779002). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu892*) 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). |
| Color Diagnostics, |
RCV000217992 | SCV001358902 | 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, |
RCV001045962 | SCV004186175 | 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 | RCV001045962 | SCV004202664 | pathogenic | Familial cancer of breast | 2023-03-15 | criteria provided, single submitter | clinical testing |