Submissions for variant NM_020381.4(PDSS2):c.1046G>A (p.Arg349Gln)

gnomAD frequency: 0.00027  dbSNP: rs201388841

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000195802	SCV000252090	likely benign	not specified	2014-05-02	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000727264	SCV000707080	uncertain significance	not provided	2017-03-27	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001335051	SCV001528089	uncertain significance	Coenzyme Q10 deficiency, primary, 3	2018-03-16	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic	RCV000727264	SCV001715901	uncertain significance	not provided	2020-06-23	criteria provided, single submitter	clinical testing
Invitae	RCV000727264	SCV002109241	uncertain significance	not provided	2022-09-24	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 349 of the PDSS2 protein (p.Arg349Gln). This variant is present in population databases (rs201388841, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PDSS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 214989). 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 PDSS2 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.
CeGaT Center for Human Genetics Tuebingen	RCV000727264	SCV002821767	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	PDSS2: BP4
Ambry Genetics	RCV002515425	SCV003601599	uncertain significance	Inborn genetic diseases	2023-01-10	criteria provided, single submitter	clinical testing	The c.1046G>A (p.R349Q) alteration is located in exon 8 (coding exon 8) of the PDSS2 gene. This alteration results from a G to A substitution at nucleotide position 1046, causing the arginine (R) at amino acid position 349 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003977544	SCV004788370	uncertain significance	PDSS2-related condition	2024-01-09	criteria provided, single submitter	clinical testing	The PDSS2 c.1046G>A variant is predicted to result in the amino acid substitution p.Arg349Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.050% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-107475977-C-T). 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.