Submissions for variant NM_005529.7(HSPG2):c.4568G>A (p.Arg1523His)

gnomAD frequency: 0.00075  dbSNP: rs147633715

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000880717	SCV001023836	likely benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000880717	SCV001475147	uncertain significance	not provided	2020-02-26	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000880717	SCV002049827	uncertain significance	not provided	2021-03-09	criteria provided, single submitter	clinical testing	The HSPG2 c.4568G>A, p.Arg1523His variant (rs147633715), to our knowledge, has not been reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 709331). This variant is found in the general population with an overall allele frequency of 0.03% (78/266,510 alleles) in the Genome Aggregation Database. The arginine at codon 1523 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.094). Based on the available information, the clinical significance of this variant is uncertain.
GeneDx	RCV000880717	SCV002074014	uncertain significance	not provided	2021-11-19	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002536824	SCV003700317	likely benign	Inborn genetic diseases	2021-06-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Revvity Omics, Revvity	RCV000880717	SCV003811317	uncertain significance	not provided	2020-04-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004735859	SCV005351216	likely benign	HSPG2-related disorder	2024-05-17	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).