Submissions for variant NM_001166108.2(PALLD):c.2084T>G (p.Leu695Arg)

gnomAD frequency: 0.00006  dbSNP: rs139375029

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000116045	SCV000149954	uncertain significance	not provided	2013-12-02	criteria provided, single submitter	clinical testing	PALLD has been only recently described in association with pancreatic cancer and the risks are not well understood. This variant is denoted PALLD c.2084T>G at the cDNA level, p.Leu695Arg (L695R) at the protein level, and results in the change of a Leucine to an Arginine (CTG>CGG). This variant has not, to our knowledge, been published in the literature. PALLD Leu695Arg was not observed at significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a non-conservative substitution of a neutral non-polar amino acid for a positive polar one, altering a position that is well conserved throughout evolution and is located in the region of Interaction with ARGBP2, SPIN90, SRC and PFN1 per UNIPROT. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the PALLD gene, remain unclear.
Invitae	RCV001083897	SCV000254733	benign	Pancreatic adenocarcinoma	2023-10-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000397936	SCV000448484	benign	Pancreatic cancer, susceptibility to, 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV002415595	SCV002726906	uncertain significance	Hereditary cancer-predisposing syndrome	2022-10-05	criteria provided, single submitter	clinical testing	The p.L695R variant (also known as c.2084T>G), located in coding exon 10 of the PALLD gene, results from a T to G substitution at nucleotide position 2084. The leucine at codon 695 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Ambry Genetics	RCV002515796	SCV003708612	uncertain significance	Inborn genetic diseases	2021-09-27	criteria provided, single submitter	clinical testing	The c.2084T>G (p.L695R) alteration is located in exon 11 (coding exon 10) of the PALLD gene. This alteration results from a T to G substitution at nucleotide position 2084, causing the leucine (L) at amino acid position 695 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.