Submissions for variant NM_024675.4(PALB2):c.693A>T (p.Lys231Asn)

dbSNP: rs876658847

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215723	SCV000274626	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-11	criteria provided, single submitter	clinical testing	The p.K231N variant (also known as c.693A>T), located in coding exon 4 of the PALB2 gene, results from an A to T substitution at nucleotide position 693. The lysine at codon 231 is replaced by asparagine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000474743	SCV000550606	uncertain significance	Familial cancer of breast	2023-09-15	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 230928). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 231 of the PALB2 protein (p.Lys231Asn).
Color Diagnostics, LLC DBA Color Health	RCV000215723	SCV001735690	uncertain significance	Hereditary cancer-predisposing syndrome	2024-01-18	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with asparagine at codon 231 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant nor has this variant has been reported as a germline mutation in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genetics and Molecular Pathology, SA Pathology	RCV000474743	SCV002556475	uncertain significance	Familial cancer of breast	2020-10-14	criteria provided, single submitter	clinical testing
GeneDx	RCV003226913	SCV003923362	uncertain significance	not provided	2023-05-02	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 19369211)