Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781689 | SCV000919942 | likely pathogenic | Familial cancer of breast | 2018-04-23 | criteria provided, single submitter | clinical testing | Variant summary: PALB2 c.3297_3298insT (p.Thr1100TyrfsX23) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.3323delA, p.Tyr1108fsX16; c.3549C>A, p.Tyr1183X). The variant was absent in 121400 control chromosomes. To our knowledge, no occurrence of c.3297_3298insT in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV000781689 | SCV003472635 | pathogenic | Familial cancer of breast | 2022-01-04 | criteria provided, single submitter | clinical testing | 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: 633344). This variant disrupts a region of the PALB2 protein in which other variant(s) (p.Tyr1183*) have been determined to be pathogenic (PMID: 17200671, 19609323, 20927582, 21165770, 21365267, 26283626, 26296701). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Thr1100Tyrfs*23) in the PALB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 87 amino acid(s) of the PALB2 protein. |
| Myriad Genetics, |
RCV000781689 | SCV004186246 | pathogenic | Familial cancer of breast | 2023-09-14 | 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 | RCV000781689 | SCV004202710 | likely pathogenic | Familial cancer of breast | 2022-09-29 | criteria provided, single submitter | clinical testing |