VCV000466603.17 - ClinVar

NM_000232.5(SGCB):c.656_657del (p.Lys219fs)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic

4 out of 5 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000232.5(SGCB):c.656_657del (p.Lys219fs)

Variation ID: 466603 Accession: VCV000466603.17

Type and length

Deletion, 2 bp

Location

Cytogenetic: 4q12 4: 52028064-52028065 (GRCh38) [ NCBI UCSC ] 4: 52894230-52894231 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 26, 2017	Sep 6, 2025	Aug 14, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000232.5:c.656_657del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000223.1:p.Lys219fs	frameshift
NM_000232.4:c.656_657delAA		frameshift
NC_000004.12:g.52028066_52028067del
NC_000004.11:g.52894232_52894233del
NG_008891.1:g.15255_15256del
LRG_204:g.15255_15256del
LRG_204t1:c.656_657del	LRG_204p1:p.Lys219fs

... more HGVS ... less HGVS

Protein change

K219fs

Other names

Canonical SPDI

NC_000004.12:52028063:TTTT:TT

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA551340682 dbSNP: rs775458201 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SGCB		-	-	GRCh38 GRCh37	548	665

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Autosomal recessive limb-girdle muscular dystrophy type 2E	Pathogenic/Likely pathogenic (5)	criteria provided, multiple submitters, no conflicts	Aug 14, 2024	RCV000530736.18

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 30, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Autosomal recessive limb-girdle muscular dystrophy type 2E	Baylor Genetics Accession: SCV004201000.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely pathogenic (Jun 05, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Autosomal recessive limb-girdle muscular dystrophy type 2E	Fulgent Genetics, Fulgent Genetics Accession: SCV002783200.2 First in ClinVar: Dec 31, 2022 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 14, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Autosomal recessive limb-girdle muscular dystrophy type 2E	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000642377.8 First in ClinVar: Dec 26, 2017 Last updated: Feb 25, 2025	Publications: PubMed (2) PubMed: 15938573‚ 18285821 Comment: show This sequence change creates a premature translational stop signal (p.Lys219Serfs*2) in the SGCB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCB are known to be pathogenic (PMID: 15938573, 18285821). This variant is present in population databases (no rsID available, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SGCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 466603). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Mar 28, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Autosomal recessive limb-girdle muscular dystrophy type 2E	Revvity Omics, Revvity Accession: SCV004238646.2 First in ClinVar: Feb 04, 2024 Last updated: Sep 06, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Apr 06, 2017) N Not contributing to aggregate classification	no assertion criteria provided	Autosomal recessive limb-girdle muscular dystrophy type 2E	Counsyl Accession: SCV000790743.3 First in ClinVar: Dec 26, 2017 Last updated: Jun 29, 2025	Comment: show 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. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Comment:

This sequence change creates a premature translational stop signal (p.Lys219Serfs*2) in the SGCB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCB are known to be pathogenic (PMID: 15938573, 18285821). This variant is present in population databases (no rsID available, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SGCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 466603). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Revised spectrum of mutations in sarcoglycanopathies.	Trabelsi M	European journal of human genetics : EJHG	2008	PMID: 18285821
Beta-sarcoglycan gene mutations in Turkey.	Balci B	Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology	2004	PMID: 15938573

Text-mined citations for rs775458201 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 07, 2025

ClinVar Genomic variation as it relates to human health

NM_000232.5(SGCB):c.656_657del (p.Lys219fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for rs775458201 ...