Submissions for variant NM_001166108.2(PALLD):c.1289G>A (p.Arg430Gln)

gnomAD frequency: 0.00016  dbSNP: rs145571230

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000116040	SCV000149949	uncertain significance	not provided	2014-02-18	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.1289G>A at the cDNA level, p.Arg430Gln (R430Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PALLD Arg430Gln was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a semi-conservative substitution in which a positive polar amino acid is replaced with a neutral polar one, altering a position that is well conserved throughout evolution and is not located in a known functional domain. In silico analyses predict this variant to have a benign effect 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.
Illumina Laboratory Services, Illumina	RCV000373110	SCV000448475	benign	Pancreatic cancer, susceptibility to, 1	2018-01-12	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.
PreventionGenetics, part of Exact Sciences	RCV003905104	SCV004719897	likely benign	PALLD-related disorder	2022-07-14	no assertion criteria provided	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).