Submissions for variant NM_005529.7(HSPG2):c.11717G>A (p.Arg3906Gln)

dbSNP: rs78944354

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000180429	SCV000232862	benign	not specified	2015-02-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756261	SCV000884015	likely benign	not provided	2017-12-28	criteria provided, single submitter	clinical testing	The HSPG2 p.Arg3906Gln variant (rs78944354) has not been reported in association with disease and is classified as benign in ClinVar (Variant ID: 198963). The p.Arg3906Gln variant is also listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.55% in the African population (identified in 119 out of 21,738 chromosomes with 1 homozygote). The arginine at codon 3906 is weakly conserved considering 12 species (Alamut software v2.10.0), and multiple species have a glutamine at this position, which suggests that this change is tolerated by evolution. Although computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: disease causing), based on the available evidence, the p.Arg3906Gln variant is classified as likely benign.
Invitae	RCV000756261	SCV001026878	benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000756261	SCV001477273	likely benign	not provided	2020-04-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000756261	SCV001794858	likely benign	not provided	2019-08-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516819	SCV003677111	likely benign	Inborn genetic diseases	2022-04-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003937638	SCV004753656	likely benign	HSPG2-related condition	2019-11-12	criteria provided, single submitter	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).