Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000454134 | SCV000538138 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-02-21 | criteria provided, single submitter | clinical testing | The c.1186dupT pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a duplication of T at nucleotide position 1186, causing a translational frameshift with a predicted alternate stop codon (p.C396Lfs*5). This alteration was identified in a French patient with a personal and family history of breast cancer (Damiola F et al. Breast Cancer Res. Treat., 2015 Dec;154:463-71). 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 | RCV000685167 | SCV000812640 | pathogenic | Familial cancer of breast | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys396Leufs*5) 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 premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26564480). ClinVar contains an entry for this variant (Variation ID: 402291). For these reasons, this variant has been classified as Pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985883 | SCV001134530 | pathogenic | not provided | 2018-10-19 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. |
Myriad Genetics, |
RCV000685167 | SCV004188551 | pathogenic | Familial cancer of breast | 2023-09-08 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |