NM_000023.4(SGCA):c.92T>C (p.Leu31Pro) AND Autosomal recessive limb-girdle muscular dystrophy type 2D

Germline classification:: Pathogenic/Likely pathogenic (7 submissions)
Last evaluated:: Nov 13, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000665054.20

Allele description [Variation Report for NM_000023.4(SGCA):c.92T>C (p.Leu31Pro)]

NM_000023.4(SGCA):c.92T>C (p.Leu31Pro)

Gene:

SGCA:sarcoglycan alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.33

Genomic location:

Preferred name:

NM_000023.4(SGCA):c.92T>C (p.Leu31Pro)

HGVS:

NC_000017.11:g.50167422T>C
NG_008889.1:g.6418T>C
NM_000023.4:c.92T>CMANE SELECT
NM_001135697.3:c.92T>C
NP_000014.1:p.Leu31Pro
NP_001129169.1:p.Leu31Pro
LRG_203t1:c.92T>C
LRG_203:g.6418T>C
NC_000017.10:g.48244783T>C
NM_000023.2:c.92T>C
NR_135553.2:n.128T>C
p.Leu31Pro

Protein change:

L31P

Links:

dbSNP: rs903823830

NCBI 1000 Genomes Browser:

rs903823830

Molecular consequence:

NM_000023.4:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001135697.3:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_135553.2:n.128T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2D (LGMDR3)
Synonyms:: ADHALINOPATHY, PRIMARY; DUCHENNE-LIKE AUTOSOMAL RECESSIVE MUSCULAR DYSTROPHY, TYPE 2; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 3
Identifiers:: MONDO: MONDO:0011968; MedGen: C2936332; Orphanet: 62; OMIM: 608099

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000789113	Counsyl	no assertion criteria provided	Likely pathogenic (Jan 11, 2017)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9032047, 22095924, 17994539, 24565866, 18285821, 12566530
SCV000937162	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 13, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9032047, 12566530, 18285821, 22095924, 29351619, 28492532
SCV001432771	Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 30, 2020)	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003931628	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004203177	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 27, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004238349	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 18, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005649529	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Caucasians	paternal	yes	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients.

Guglieri M, Magri F, D'Angelo MG, Prelle A, Morandi L, Rodolico C, Cagliani R, Mora M, Fortunato F, Bordoni A, Del Bo R, Ghezzi S, Pagliarani S, Lucchiari S, Salani S, Zecca C, Lamperti C, Ronchi D, Aguennouz M, Ciscato P, Di Blasi C, Ruggieri A, et al.

Hum Mutat. 2008 Feb;29(2):258-66.

PubMed [citation]

PMID:: 17994539

Unveiling the degradative route of the V247M α-sarcoglycan mutant responsible for LGMD-2D.

Bianchini E, Fanin M, Mamchaoui K, Betto R, Sandonà D.

Hum Mol Genet. 2014 Jul 15;23(14):3746-58. doi: 10.1093/hmg/ddu088. Epub 2014 Feb 23.

PubMed [citation]

PMID:: 24565866
PMCID:: PMC4065151

See all PubMed Citations (9)

Details of each submission

From Counsyl, SCV000789113.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000937162.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 31 of the SGCA protein (p.Leu31Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 9032047, 12566530, 18285821, 29351619). ClinVar contains an entry for this variant (Variation ID: 550333). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SGCA protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SGCA function (PMID: 22095924, 29351619). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN, SCV001432771.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasians	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	blood	not provided		1	not provided	1	not provided

From Genome-Nilou Lab, SCV003931628.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004203177.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV004238349.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV005649529.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 6, 2025

Relating variation to medicine