Submissions for variant NM_001166108.2(PALLD):c.539C>T (p.Thr180Ile)

gnomAD frequency: 0.00071  dbSNP: rs146387060

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000116055	SCV000149964	uncertain significance	not provided	2014-02-25	criteria provided, single submitter	clinical testing	This variant is denoted PALLD c.539C>T at the cDNA level, p.Thr180Ile (T180I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACA>ATA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PALLD Thr180Ile was observed with an allele frequency of 0.2% (11/4406) in African Americans in the NHLBI Exome Sequencing Project. Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution and is likely to affect protein integrity. PALLD Thr180Ile occurs at a position that is well conserved across species and is not located in a known functional domain. In silico analyses are inconsistent regarding 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.
Illumina Laboratory Services, Illumina	RCV000400101	SCV000448464	likely benign	Pancreatic cancer, susceptibility to, 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Ambry Genetics	RCV004019620	SCV002650975	uncertain significance	not specified	2022-09-26	criteria provided, single submitter	clinical testing	The p.T180I variant (also known as c.539C>T), located in coding exon 1 of the PALLD gene, results from a C to T substitution at nucleotide position 539. The threonine at codon 180 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. 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.
PreventionGenetics, part of Exact Sciences	RCV003905105	SCV004722189	likely benign	PALLD-related disorder	2019-06-21	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).