NM_001130987.2(DYSF):c.5684T>A (p.Val1895Glu) AND Qualitative or quantitative defects of dysferlin

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 20, 2024
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:: RCV003738747.3

Allele description [Variation Report for NM_001130987.2(DYSF):c.5684T>A (p.Val1895Glu)]

NM_001130987.2(DYSF):c.5684T>A (p.Val1895Glu)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.5684T>A (p.Val1895Glu)

HGVS:

NC_000002.12:g.71669646T>A
NG_008694.1:g.221024T>A
NM_001130455.2:c.5570T>A
NM_001130976.2:c.5525T>A
NM_001130977.2:c.5588T>A
NM_001130978.2:c.5630T>A
NM_001130979.2:c.5660T>A
NM_001130980.2:c.5618T>A
NM_001130981.2:c.5681T>A
NM_001130982.2:c.5663T>A
NM_001130983.2:c.5633T>A
NM_001130984.2:c.5591T>A
NM_001130985.2:c.5621T>A
NM_001130986.2:c.5528T>A
NM_001130987.2:c.5684T>AMANE SELECT
NM_003494.4:c.5567T>A
NP_001123927.1:p.Val1857Glu
NP_001124448.1:p.Val1842Glu
NP_001124449.1:p.Val1863Glu
NP_001124450.1:p.Val1877Glu
NP_001124451.1:p.Val1887Glu
NP_001124452.1:p.Val1873Glu
NP_001124453.1:p.Val1894Glu
NP_001124454.1:p.Val1888Glu
NP_001124455.1:p.Val1878Glu
NP_001124456.1:p.Val1864Glu
NP_001124457.1:p.Val1874Glu
NP_001124458.1:p.Val1843Glu
NP_001124459.1:p.Val1895Glu
NP_003485.1:p.Val1856Glu
LRG_845t1:c.5567T>A
LRG_845t2:c.5684T>A
LRG_845:g.221024T>A
LRG_845p1:p.Val1856Glu
LRG_845p2:p.Val1895Glu
NC_000002.11:g.71896776T>A

Protein change:

V1842E

Molecular consequence:

NM_001130455.2:c.5570T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130976.2:c.5525T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130977.2:c.5588T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130978.2:c.5630T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130979.2:c.5660T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130980.2:c.5618T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130981.2:c.5681T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130982.2:c.5663T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130983.2:c.5633T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130984.2:c.5591T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130985.2:c.5621T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130986.2:c.5528T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130987.2:c.5684T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003494.4:c.5567T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Qualitative or quantitative defects of dysferlin
Synonyms:: Dysferlinopathy
Identifiers:: MONDO: MONDO:0016145; MedGen: C2931687

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004548567	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 20, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30098242, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004548567

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 20, 2024)

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

[Analysis of DYSF gene mutations in two pedigrees affected with limb-girdle muscular dystrophy type 2B].

Liu Z, Liao H, Zhang X, Zhang H, Liu H, Wang H, Liu S.

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018 Aug 10;35(4):498-501. doi: 10.3760/cma.j.issn.1003-9406.2018.04.008. Chinese.

PubMed [citation]

PMID:: 30098242

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004548567.2

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

Description

This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1856 of the DYSF protein (p.Val1856Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 30098242). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 expected to disrupt DYSF protein function with a positive predictive value of 80%. 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.

#	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: Mar 11, 2025

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