NM_001130987.2(DYSF):c.4911+1G>T AND Neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 3, 2023
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:: RCV001223491.10

Allele description [Variation Report for NM_001130987.2(DYSF):c.4911+1G>T]

NM_001130987.2(DYSF):c.4911+1G>T

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.4911+1G>T

HGVS:

NC_000002.12:g.71659034G>T
NG_008694.1:g.210412G>T
NM_001130455.2:c.4797+1G>T
NM_001130976.2:c.4752+1G>T
NM_001130977.2:c.4815+1G>T
NM_001130978.2:c.4857+1G>T
NM_001130979.2:c.4887+1G>T
NM_001130980.2:c.4845+1G>T
NM_001130981.2:c.4908+1G>T
NM_001130982.2:c.4890+1G>T
NM_001130983.2:c.4860+1G>T
NM_001130984.2:c.4818+1G>T
NM_001130985.2:c.4848+1G>T
NM_001130986.2:c.4755+1G>T
NM_001130987.2:c.4911+1G>TMANE SELECT
NM_003494.4:c.4794+1G>T
LRG_845t1:c.4794+1G>T
LRG_845t2:c.4911+1G>T
LRG_845:g.210412G>T
NC_000002.11:g.71886164G>T
NM_003494.3:c.4794+1G>T

Links:

dbSNP: rs777216777

Molecular consequence:

NM_001130455.2:c.4797+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130976.2:c.4752+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130977.2:c.4815+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130978.2:c.4857+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130979.2:c.4887+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130980.2:c.4845+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130981.2:c.4908+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130982.2:c.4890+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130983.2:c.4860+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130984.2:c.4818+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130985.2:c.4848+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130986.2:c.4755+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001130987.2:c.4911+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003494.4:c.4794+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Neuromuscular disease caused by qualitative or quantitative defects of dysferlin
Synonyms:: Qualitative or quantitative defects of dysferlin
Identifiers:: MONDO: MONDO:0016145; MedGen: C2931687

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001395643	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 3, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23243261, 16199547, 17698709, 20301480, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001395643

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 3, 2023)

germline

clinical testing

PubMed (5)
[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

Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B.

Takahashi T, Aoki M, Suzuki N, Tateyama M, Yaginuma C, Sato H, Hayasaka M, Sugawara H, Ito M, Abe-Kondo E, Shimakura N, Ibi T, Kuru S, Wakayama T, Sobue G, Fujii N, Saito T, Matsumura T, Funakawa I, Mukai E, Kawanami T, Morita M, et al.

J Neurol Neurosurg Psychiatry. 2013 Apr;84(4):433-40. doi: 10.1136/jnnp-2011-301339. Epub 2012 Dec 15.

PubMed [citation]

PMID:: 23243261
PMCID:: PMC3595148

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001395643.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 282513). Disruption of this splice site has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 23243261). This variant is present in population databases (rs777216777, gnomAD 0.004%). This sequence change affects a donor splice site in intron 43 of the DYSF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480).

#	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 15, 2026

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Relating variation to medicine