Submissions for variant NM_024675.4(PALB2):c.2360C>T (p.Thr787Ile)

gnomAD frequency: 0.00002  dbSNP: rs201042302

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000197564	SCV000255085	likely benign	Familial cancer of breast	2024-01-23	criteria provided, single submitter	clinical testing
Cancer Genetics Laboratory, Peter MacCallum Cancer Centre	RCV000197564	SCV000268012	uncertain significance	Familial cancer of breast	2015-06-01	criteria provided, single submitter	case-control
Ambry Genetics	RCV000216753	SCV000273009	likely benign	Hereditary cancer-predisposing syndrome	2023-01-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000236931	SCV000294068	uncertain significance	not provided	2019-04-26	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with breast cancer (Thompson 2015, Zhang 2017); This variant is associated with the following publications: (PMID: 25256751, 28825143, 26283626, 25230021)
Counsyl	RCV000197564	SCV000488211	uncertain significance	Familial cancer of breast	2016-01-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000216753	SCV000903032	likely benign	Hereditary cancer-predisposing syndrome	2016-07-18	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000216753	SCV002530691	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-25	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000197564	SCV004019172	uncertain significance	Familial cancer of breast	2023-03-30	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000236931	SCV004222298	uncertain significance	not provided	2023-06-08	criteria provided, single submitter	clinical testing	In the published literature, this variant has been reported in individuals with breast cancer (PMIDs: 28825143 (2017), 26283626 (2015)) and colorectal cancer (PMID: 28944238 (2017)). In a large breast cancer association study, this variant was found in both individuals with breast cancer as well as unaffected individuals (PMID: 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/PALB2)). The frequency of this variant in the general population, 0.0011 (16/14424 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tolls for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Leiden Open Variation Database	RCV001030299	SCV001193215	uncertain significance	Carcinoma of colon	2017-01-31	no assertion criteria provided	curation	Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Melissa DeRycke.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000236931	SCV002035886	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000236931	SCV002037346	uncertain significance	not provided		no assertion criteria provided	clinical testing