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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000544134	SCV000642381	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2E	2024-03-04	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 with a negative predictive value of 80%. 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	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2E	2024-02-01	criteria provided, single submitter	clinical testing	The missense c.544A>C (p.Thr182Pro) variant in SGCB gene has been reported previously in multiple individuals affected with sarcoglycanopathy and limb-girdle muscular dystrophies (LGMDs) (Chakravorty et al., 2020; Bardhan et al., 2022). Other variant(s) that disrupt this residue have been observed in individuals with SGCB-related conditions (Duggan et al., 1997). Additional functional studies will be required to prove the pathogenicity of this variant conclusively.
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	flagged submission	clinical testing