Submissions for variant NM_024675.4(PALB2):c.3053A>C (p.Glu1018Ala)

dbSNP: rs1567212910

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000699589	SCV000828307	uncertain significance	Familial cancer of breast	2024-02-24	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1018 of the PALB2 protein (p.Glu1018Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 25186627). ClinVar contains an entry for this variant (Variation ID: 576952). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PALB2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health	RCV000773319	SCV000907011	uncertain significance	Hereditary cancer-predisposing syndrome	2018-12-13	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004696981	SCV005197072	uncertain significance	not provided	2022-11-14	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV000699589	SCV001193335	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.