Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000023.4(SGCA):c.203G>A (p.Gly68Glu)

CA400177350

1052453 (ClinVar)

Gene: SGCA (HGNC:6442)

Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)

Inheritance Mode: Autosomal recessive inheritance

UUID: d3e15f56-7d4b-4607-9945-4d7c97d2cf24

Approved on: 2026-04-29

Published on: 2026-05-07

HGVS expressions

NM_000023.4(SGCA):c.203G>A (p.Gly68Glu)

NM_000023.4:c.203G>A

NC_000017.11:g.50167627G>A

CM000679.2:g.50167627G>A

NC_000017.10:g.48244988G>A

CM000679.1:g.48244988G>A

NC_000017.9:g.45599987G>A

NG_008889.1:g.6623G>A

ENST00000504073.2:c.203G>A

ENST00000511303.6:n.38-320G>A

ENST00000512526.2:c.203G>A

ENST00000682109.1:c.83G>A

ENST00000683294.1:c.203G>A

ENST00000262018.8:c.203G>A

ENST00000262018.7:c.203G>A

ENST00000344627.10:c.203G>A

ENST00000502555.5:c.157+140G>A

ENST00000511303.5:c.34-320G>A

ENST00000512526.1:c.47G>A

ENST00000513821.5:c.203G>A

ENST00000513942.5:n.104-320G>A

ENST00000514934.1:c.*18+140G>A

NM_000023.2:c.203G>A

NM_001135697.1:c.203G>A

NM_000023.3:c.203G>A

NM_001135697.2:c.203G>A

NR_135553.1:n.259G>A

NM_001135697.3:c.203G>A

NR_135553.2:n.239G>A

Likely Pathogenic

PM2_Supporting PS3_Moderate PP4 PP3 PM3

Evidence Links 0

Expert Panel

Limb Girdle Muscular Dystrophy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SGCA Version 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Limb Girdle Muscular Dystrophy VCEP

The NM_000023.4: c.203G>A variant in SGCA is a missense variant predicted to cause substitution of glycine by glutamic acid at amino acid 68, p.(Gly68Glu). This variant has been detected in at least two individuals with limb-girdle muscular dystrophy, where it was reported in unconfirmed phase with pathogenic variant in both cases (c.229C>T p.(Arg77Cys), 0.5 pts, PMID: 7663524; c.739G>A p.(Val247Met), 0.5 pts, GRASP-LGMD Consortium internal data communication) (PM3). At least one of these patients displayed progressive limb girdle muscle weakness and reduced alpha-sarcoglycan protein expression, which is highly specific for SGCA-related LGMD; however, the absence of variants in other sarcoglycan genes was not confirmed (PP4; PMID: 7663524). This variant is absent from gnomAD v4.1.1 (PM2_Supporting). In vitro assay in an heterologous cell system has demonstrated that this variant disrupts membrane localization of the sarcoglycan complex (PS3_Moderate, Washington University internal data). The computational predictor REVEL gives a score of 0.774, which is above the threshold of 0.7, evidence that correlates with impact to SGCA function (PP3). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 2.0.0; 04/29/2026): PM3, PP4, PM2_Supporting, PS3_Moderate, PP3.

PM2_Supporting

This variant is absent from gnomAD v4.1.1 (PM2_Supporting).

PS3_Moderate

In vitro assay in an heterologous cell system has demonstrated that this variant disrupts membrane localization of the sarcoglycan complex (PS3_Moderate, Washington University internal data). Variant was tested by Gabe Haller's team using their previously reported approach for SGCB variants. The assay has been clinically validated with over 11 control variants. The variant presented a score <-0.5 (-1), which is the threshold for non-functional variants that was used for SGCB. We don't currently have a score for this variant in the complementary Yale assay

PP4

At least one patient with this variant displayed progressive limb girdle muscle weakness and reduced alpha-sarcoglycan protein expression, which is highly specific for SGCA-related LGMD; however, the absence of variants in other sarcoglycan genes was not confirmed (PP4; PMID: 7663524).

PP3

The computational predictor REVEL gives a score of 0.774, which is above the threshold of 0.7, evidence that correlates with impact to SGCA function (PP3).

PM3

This variant has been detected in at least two individuals with limb-girdle muscular dystrophy, where it was reported in unconfirmed phase with pathogenic variant in both cases (c.229C>T p.(Arg77Cys), 0.5 pts, PMID: 7663524; c.739G>A p.(Val247Met), 0.5 pts, GRASP-LGMD Consortium internal data communication) (PM3). cannot check co-occurrence - absent from gnomAD v2 both variants classified as P independently Invitae is only submitter in ClinVar

Curation History

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