Evidence Repository
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.191T>C (p.Ile64Thr)

CA308788

202088 (ClinVar)

Gene: SGCD
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: e8316a20-ad88-4c2b-a2ec-baba843041a7
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_000337.6:c.191T>C
NM_000337.6(SGCD):c.191T>C (p.Ile64Thr)
NC_000005.10:g.156344676T>C
CM000667.2:g.156344676T>C
NC_000005.9:g.155771686T>C
CM000667.1:g.155771686T>C
NC_000005.8:g.155704264T>C
NG_008693.2:g.479333T>C
ENST00000337851.9:c.191T>C
ENST00000337851.8:c.191T>C
ENST00000435422.7:c.188T>C
ENST00000517913.5:c.191T>C
ENST00000524347.2:c.191T>C
NM_000337.5:c.191T>C
NM_001128209.1:c.188T>C
NM_172244.2:c.191T>C
NM_001128209.2:c.188T>C
NM_172244.3:c.191T>C
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Uncertain Significance

Not Met criteria codes 26
BA1 PS4 PS2 PS3 PS1 PP4 PP1 PP3 PP2 PM3 PM1 PM4 PM5 PM6 PM2 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PVS1

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.191T>C variant in SGCD is a missense variant predicted to cause substitution of isoleucine by threonine at amino acid 64 (p.Ile64Thr). The highest minor allele frequency of this variant is 0.0001293 in the Admixed American population of gnomAD v2.1.1 (4/30926 exome chromosomes), which is greater than the LGMD VCEP threshold (0.00009) for PM2_Supporting (criterion not met). The computational predictor REVEL gives a score of 0.63 (PP3, BP4 not met). In summary, there is currently insufficient evidence to determine whether this variant is pathogenic or benign and it is 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): no codes applied.
Not Met criteria codes
BA1
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
PS2
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
PP3
The computational predictor REVEL gives a score of 0.63, which is lesser than the threshold of >=0.7, evidence that does not predict a damaging effect on SGCD function (PP3 not met).
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
c.190A>G (p.Ile64Val) is VUS in ClinVar
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest minor allele frequency of this variant is 0.0001293 in the Admixed American population of gnomAD v2.1.1 (4/30926 exome chromosomes), which is greater than the LGMD VCEP threshold (0.00009) for PM2_Supporting (criterion not met).
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
The highest population minor allele frequency in gnomAD v2.1.1 is 0.0005 (4/6676 alleles) in the Other population, which is equal to the ClinGen LGMD VCEP threshold (≥0.001) for BS1
BS2
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
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
The computational predictor REVEL gives a score of 0.63, which is greater than the threshold of ≤0.10, evidence that does not predict a damaging effect on SGCD function (BP4 not met).
BP1
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
Curation History
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