Submissions for variant NM_002857.4(PEX19):c.115C>T (p.Pro39Ser)

dbSNP: rs144256391

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000595443	SCV000705674	uncertain significance	not provided	2017-12-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763753	SCV000894639	uncertain significance	Peroxisome biogenesis disorder 12A (Zellweger)	2021-11-22	criteria provided, single submitter	clinical testing
Invitae	RCV000763753	SCV000949175	uncertain significance	Peroxisome biogenesis disorder 12A (Zellweger)	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 39 of the PEX19 protein (p.Pro39Ser). This variant is present in population databases (rs144256391, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with PEX19-related conditions. ClinVar contains an entry for this variant (Variation ID: 499937). 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 not expected to disrupt PEX19 protein function. 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.
Illumina Laboratory Services, Illumina	RCV000763753	SCV001257035	uncertain significance	Peroxisome biogenesis disorder 12A (Zellweger)	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen	RCV000595443	SCV001501931	uncertain significance	not provided	2020-07-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002532492	SCV003583600	uncertain significance	Inborn genetic diseases	2022-04-13	criteria provided, single submitter	clinical testing	The c.115C>T (p.P39S) alteration is located in exon 2 (coding exon 2) of the PEX19 gene. This alteration results from a C to T substitution at nucleotide position 115, causing the proline (P) at amino acid position 39 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003980089	SCV004794009	uncertain significance	PEX19-related disorder	2024-01-22	criteria provided, single submitter	clinical testing	The PEX19 c.115C>T variant is predicted to result in the amino acid substitution p.Pro39Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.062% of alleles in individuals of Latino descent in gnomAD, which may be too common to be an unreported cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.