NM_000232.5(SGCB):c.691G>A (p.Gly231Ser) AND Autosomal recessive limb-girdle muscular dystrophy type 2E

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 21, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003030838.2

Allele description [Variation Report for NM_000232.5(SGCB):c.691G>A (p.Gly231Ser)]

NM_000232.5(SGCB):c.691G>A (p.Gly231Ser)

Gene:

SGCB:sarcoglycan beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_000232.5(SGCB):c.691G>A (p.Gly231Ser)

HGVS:

NC_000004.12:g.52028030C>T
NG_008891.1:g.15290G>A
NM_000232.5:c.691G>AMANE SELECT
NP_000223.1:p.Gly231Ser
NP_000223.1:p.Gly231Ser
LRG_204t1:c.691G>A
LRG_204:g.15290G>A
LRG_204p1:p.Gly231Ser
NC_000004.11:g.52894196C>T
NM_000232.4:c.691G>A

Protein change:

G231S

Molecular consequence:

NM_000232.5:c.691G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2E (LGMDR4)
Synonyms:: Limb-girdle muscular dystrophy, type 2E; Muscular dystrophy limb-girdle with beta-sarcoglycan deficiency; Beta-sarcoglycan limb-girdle muscular dystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011423; MedGen: C1858593; Orphanet: 119; OMIM: 604286

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
SCV003310677	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 21, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32875335, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003310677

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 21, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy.

Alonso-Pérez J, González-Quereda L, Bello L, Guglieri M, Straub V, Gallano P, Semplicini C, Pegoraro E, Zangaro V, Nascimento A, Ortez C, Comi GP, Dam LT, De Visser M, van der Kooi AJ, Garrido C, Santos M, Schara U, Gangfuß A, Løkken N, Storgaard JH, Vissing J, et al.

Brain. 2020 Sep 1;143(9):2696-2708. doi: 10.1093/brain/awaa228. Erratum in: Brain. 2023 Jan 5;146(1):e9. doi: 10.1093/brain/awac371.

PubMed [citation]

PMID:: 32875335

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

Details of each submission

From Invitae, SCV003310677.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 32875335). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 231 of the SGCB protein (p.Gly231Ser).

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine