The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000337.6(SGCD):c.91C>G (p.Arg31Gly)

CA200046

192194 (ClinVar)

Gene: SGCD
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
UUID: 5e45fe40-f1ea-4229-9008-ec7c4fb9537f
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_000337.6:c.91C>G
NM_000337.6(SGCD):c.91C>G (p.Arg31Gly)
NC_000005.10:g.156344576C>G
CM000667.2:g.156344576C>G
NC_000005.9:g.155771586C>G
CM000667.1:g.155771586C>G
NC_000005.8:g.155704164C>G
NG_008693.2:g.479233C>G
ENST00000337851.9:c.91C>G
ENST00000337851.8:c.91C>G
ENST00000435422.7:c.88C>G
ENST00000517913.5:c.91C>G
ENST00000524347.2:c.91C>G
NM_000337.5:c.91C>G
NM_001128209.1:c.88C>G
NM_172244.2:c.91C>G
NM_001128209.2:c.88C>G
NM_172244.3:c.91C>G
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Uncertain Significance

Met criteria codes 2
PM2_Supporting PP3
Not Met criteria codes 24
PM3 PM1 PM5 PM4 PM6 PVS1 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS4 PS3 PS1 PP4 PP1 PP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SGCD Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Limb Girdle Muscular Dystrophy VCEP
The NM_000337.6: c.91C>G variant in SGCD is a missense variant predicted to cause substitution of arginine by glycine at amino acid 31 (p.Arg31Gly). This variant is absent from gnomAD v2.1.1 and v4.1.0 genomes (note that the variant fails filter in exome data, suggesting it may be a sequencing artifact) (PM2_Supporting). The computational predictor REVEL gives a score of 0.85, which is above the threshold of ≥0.70, evidence that correlates with impact to SGCD function (PP3). In summary, this variant meets the criteria to be classified as a variant of uncertain significance 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 1.0.0; 01/08/2025): PM2_Supporting, PP3.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v4.1.0 genomes (note that the variant fails filter in exome data, suggesting it may be a sequencing artifact) (PM2_Supporting).
PP3
The computational predictor REVEL gives a score of 0.854, which is above the threshold of ≥0.70, evidence that correlates with impact to SGCD function (PP3).
Not Met criteria codes
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
c.91C>T (p.Arg31Trp) = VUS, c.92G>A (p.Arg31Gln) conflicting but mostly VUS
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The filtering allele frequency (the lower threshold of the 95% CI of 194/241742) of the c.91C>G (p.Arg31Gly) variant in SGCD is 0.0031 for African/African American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen Limb-Girdle Muscular Dystrophy threshold (0.002) for BA1, and therefore meets this criterion (BA1). ARC: variant fails filter in exome data and is not found in genomes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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