ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.196C>T (p.Gln66Ter) (rs180177083)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163078 SCV000213579 pathogenic Hereditary cancer-predisposing syndrome 2018-08-06 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000114503 SCV000253937 pathogenic Familial cancer of breast 2019-11-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln66*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in families affected with breast and ovarian cancer (PMID: 21285249, 21409391, 23448497, 26534844). ClinVar contains an entry for this variant (Variation ID: 126629). Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). For these reasons, this variant has been classified as Pathogenic.
Cancer Genetics Laboratory,Peter MacCallum Cancer Centre RCV000114503 SCV000267959 likely pathogenic Familial cancer of breast 2015-06-01 criteria provided, single submitter case-control
GeneDx RCV000235795 SCV000292642 pathogenic not provided 2018-08-24 criteria provided, single submitter clinical testing This variant is denoted PALB2 c.196C>T at the cDNA level and p.Gln66Ter (Q66X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in familial breast cancer patients and is considered pathogenic (Casadei 2011, Wong 2011, Teo 2013, Antoniou 2014, Thompson 2015).
Counsyl RCV000114503 SCV000487889 likely pathogenic Familial cancer of breast 2015-12-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235795 SCV000601747 pathogenic not provided 2017-01-31 criteria provided, single submitter clinical testing
Color RCV000163078 SCV000685912 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588616 SCV000699549 pathogenic Hereditary breast and ovarian cancer syndrome 2016-04-01 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes nonsense mutation involving a conserved nucleotide predicted to cause a truncated PALB2 protein, a known disease mechanism for HBOC. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP), but has been reported in multiple affected individuals (primarily from Australia) via publications and reputable databases/clinical laboratories cite the variant with a classification of "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
True Health Diagnostics RCV000163078 SCV000805276 pathogenic Hereditary cancer-predisposing syndrome 2018-04-09 no assertion criteria provided clinical testing
Leiden Open Variation Database RCV000114503 SCV001192939 pathogenic Familial cancer of breast 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.

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