Submissions for variant NM_000232.5(SGCB):c.544A>C (p.Thr182Pro)

gnomAD frequency: 0.00001  dbSNP: rs751427686

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000544134	SCV000642381	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2E	2023-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 182 of the SGCB protein (p.Thr182Pro). This variant is present in population databases (rs751427686, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of SGCB-related conditions (PMID: 33250842, 35416532; Invitae). ClinVar contains an entry for this variant (Variation ID: 466604). 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 SGCB protein function. This variant disrupts the p.Thr182 amino acid residue in SGCB. Other variant(s) that disrupt this residue have been observed in individuals with SGCB-related conditions (PMID: 9032047), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000544134	SCV002019196	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2E	2023-10-02	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV000544134	SCV002073027	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2E		criteria provided, single submitter	clinical testing	The missense variant p.T182P in SGCB (NM_000232.4) has been previously submitted in ClinVar as variant of uncertain significance.The variant has not been previously reported in literature in affected individuals. A different missense substitution at this codon (p.Thr182Ala) has been reported in the compound heterozygous state with a pathogenic variant in an individual affected with SGCB-related disease (Duggan DJ et al). The p.T182P variant is observed in 3/30,612 (0.0098%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.T182P missense variant is predicted to be damaging by both SIFT and PolyPhen2. The threonine residue at codon 182 of SGCB is conserved in all mammalian species. The nucleotide c.544 in SGCB is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Baylor Genetics	RCV000544134	SCV004200998	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2E	2024-02-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV004568823	SCV005051226	likely pathogenic	not provided	2024-05-01	criteria provided, single submitter	clinical testing	SGCB: PM3:Strong, PM2, PM5, PP3
Natera, Inc.	RCV000544134	SCV002082980	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2E	2019-11-11	no assertion criteria provided	clinical testing