NM_000023.4(SGCA):c.1015G>A (p.Gly339Arg) AND Autosomal recessive limb-girdle muscular dystrophy type 2D

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Feb 8, 2023
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:: RCV000815330.10

Allele description

NM_000023.4(SGCA):c.1015G>A (p.Gly339Arg)

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.1015G>A (p.Gly339Arg)

HGVS:

NC_000017.11:g.50175288G>A
NG_008889.1:g.14284G>A
NM_000023.4:c.1015G>AMANE SELECT
NM_001135697.3:c.643G>A
NP_000014.1:p.Gly339Arg
NP_001129169.1:p.Gly215Arg
LRG_203t1:c.1015G>A
LRG_203:g.14284G>A
NC_000017.10:g.48252649G>A
NM_000023.2:c.1015G>A
NM_000023.3:c.1015G>A
NR_135553.2:n.842G>A

Protein change:

G215R

Links:

dbSNP: rs540254057

NCBI 1000 Genomes Browser:

rs540254057

Molecular consequence:

NM_000023.4:c.1015G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001135697.3:c.643G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_135553.2:n.842G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2D (LGMDR3)
Synonyms:: ADHALINOPATHY, PRIMARY; Limb-girdle muscular dystrophy, type 2D; Muscular dystrophy limb-girdle with alpha-sarcoglycan; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011968; MedGen: C2936332; Orphanet: 62; OMIM: 608099

Recent activity

Clear Turn Off Turn On

ras [Mytilus edulis]
ras [Mytilus edulis]
gi|50726950|gb|AAT81171.1|

Protein

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
SCV000955779	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 6, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002087589	Natera, Inc.	no assertion criteria provided	Uncertain significance (Nov 11, 2019)	germline	clinical testing
SCV003827554	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 19, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003931708	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 8, 2023)	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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Invitae, SCV000955779.3

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 339 of the SGCA protein (p.Gly339Arg). This variant is present in population databases (rs540254057, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SGCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 282864). 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 SGCA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Natera, Inc., SCV002087589.1

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

#	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 Revvity Omics, Revvity, SCV003827554.2

#	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 Genome-Nilou Lab, SCV003931708.1

#	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: May 7, 2024

ClinVar

Relating variation to medicine