Submissions for variant NM_024675.4(PALB2):c.1743A>G (p.Leu581=)

gnomAD frequency: 0.00002  dbSNP: rs180177105

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000220391	SCV000276339	likely benign	Hereditary cancer-predisposing syndrome	2015-06-09	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001030257	SCV000561154	likely benign	Familial cancer of breast	2024-01-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000220391	SCV000685898	likely benign	Hereditary cancer-predisposing syndrome	2017-03-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000829294	SCV000971010	likely benign	not provided	2018-05-04	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Sema4, Sema4	RCV000220391	SCV002530643	likely benign	Hereditary cancer-predisposing syndrome	2022-03-05	criteria provided, single submitter	curation
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492440	SCV004239552	likely benign	Breast and/or ovarian cancer	2022-11-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004529919	SCV004726920	likely benign	PALB2-related disorder	2019-06-18	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Leiden Open Variation Database	RCV001030257	SCV001193151	likely benign	Familial cancer of breast	2019-05-13	no assertion criteria provided	curation	Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.