Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000472709 | SCV000550789 | pathogenic | Familial cancer of breast | 2016-09-04 | criteria provided, single submitter | clinical testing | This sequence change deletes 2 nucleotides from exon 4 of the PALB2 mRNA (c.953_954delGT), causing a frameshift at codon 318. This creates a premature translational stop signal (p.Ser318Ilefs*2) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in PALB2 are known to be pathogenic (PMID: 25099575, 17200668). For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV000775927 | SCV000910418 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant deletes 2 nucleotides in exon 4 of the PALB2 gene, creating a frameshift and 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. |
| Ambry Genetics | RCV000775927 | SCV002688281 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-12-21 | criteria provided, single submitter | clinical testing | The c.953_954delGT pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a deletion of two nucleotides at nucleotide positions 953 to 954, causing a translational frameshift with a predicted alternate stop codon (p.S318Ifs*2). 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, |
RCV000472709 | SCV004186136 | pathogenic | Familial cancer of breast | 2023-09-07 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV000472709 | SCV004202721 | likely pathogenic | Familial cancer of breast | 2022-08-28 | criteria provided, single submitter | clinical testing |