Submissions for variant NM_005529.7(HSPG2):c.12110G>T (p.Arg4037Leu)

dbSNP: rs143015575

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001101523	SCV001258139	uncertain significance	Schwartz-Jampel syndrome	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.
Illumina Laboratory Services, Illumina	RCV001101524	SCV001258140	uncertain significance	Lethal Kniest-like syndrome	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811656	SCV001471928	uncertain significance	not provided	2020-01-20	criteria provided, single submitter	clinical testing	The p.Arg4037Leu variant (rs143015575) has been previously identified in a single patient who was part of a cohort diagnosed with idiopathic scoliosis (Baschal 2014). However the exact contribution of this variant to the clinical phenotype of the patient described Baschal (2014) is unclear. This variant is found in the general population with an overall allele frequency of 0.092 % (207/ 224,824 alleles) in the Genome Aggregation Database. The arginine at codon 4037 is moderately conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: probably damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg4037Leu variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001811656	SCV002381104	likely benign	not provided	2025-01-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001811656	SCV005078488	uncertain significance	not provided	2023-12-05	criteria provided, single submitter	clinical testing	Identified in a patient with idiopathic scoliosis in published literature (PMID: 25504735); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25504735)
PreventionGenetics, part of Exact Sciences	RCV004734014	SCV005360901	likely benign	HSPG2-related disorder	2024-06-04	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).