NM_001130987.2(DYSF):c.3170G>A (p.Arg1057Gln) AND Qualitative or quantitative defects of dysferlin

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 31, 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:: RCV001988775.4

Allele description [Variation Report for NM_001130987.2(DYSF):c.3170G>A (p.Arg1057Gln)]

NM_001130987.2(DYSF):c.3170G>A (p.Arg1057Gln)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.3170G>A (p.Arg1057Gln)

HGVS:

NC_000002.12:g.71570683G>A
NG_008694.1:g.122061G>A
NM_001130455.2:c.3119G>A
NM_001130976.2:c.3074G>A
NM_001130977.2:c.3074G>A
NM_001130978.2:c.3116G>A
NM_001130979.2:c.3209G>A
NM_001130980.2:c.3167G>A
NM_001130981.2:c.3167G>A
NM_001130982.2:c.3212G>A
NM_001130983.2:c.3119G>A
NM_001130984.2:c.3077G>A
NM_001130985.2:c.3170G>A
NM_001130986.2:c.3077G>A
NM_001130987.2:c.3170G>AMANE SELECT
NM_003494.3:c.3116G>A
NM_003494.4:c.3116G>A
NP_001123927.1:p.Arg1040Gln
NP_001124448.1:p.Arg1025Gln
NP_001124449.1:p.Arg1025Gln
NP_001124450.1:p.Arg1039Gln
NP_001124451.1:p.Arg1070Gln
NP_001124452.1:p.Arg1056Gln
NP_001124453.1:p.Arg1056Gln
NP_001124454.1:p.Arg1071Gln
NP_001124455.1:p.Arg1040Gln
NP_001124456.1:p.Arg1026Gln
NP_001124457.1:p.Arg1057Gln
NP_001124458.1:p.Arg1026Gln
NP_001124459.1:p.Arg1057Gln
NP_003485.1:p.Arg1039Gln
LRG_845t1:c.3116G>A
LRG_845t2:c.3170G>A
LRG_845:g.122061G>A
LRG_845p1:p.Arg1039Gln
LRG_845p2:p.Arg1057Gln
NC_000002.11:g.71797813G>A

Protein change:

R1025Q

Links:

dbSNP: rs149617331

NCBI 1000 Genomes Browser:

rs149617331

Molecular consequence:

NM_001130455.2:c.3119G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130976.2:c.3074G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130977.2:c.3074G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130978.2:c.3116G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130979.2:c.3209G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130980.2:c.3167G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130981.2:c.3167G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130982.2:c.3212G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130983.2:c.3119G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130984.2:c.3077G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130985.2:c.3170G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130986.2:c.3077G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130987.2:c.3170G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003494.4:c.3116G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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myb family transcription factor APL-like [Cucurbita maxima]
myb family transcription factor APL-like [Cucurbita maxima]
gi|1281003969|ref|XP_022985858.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002283918	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 31, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17070050, 25591676, 31268554, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002283918

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 31, 2023)

germline

clinical testing

PubMed (4)
[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

Dysferlin expression in monocytes: a source of mRNA for mutation analysis.

De Luna N, Freixas A, Gallano P, Caselles L, Rojas-García R, Paradas C, Nogales G, Dominguez-Perles R, Gonzalez-Quereda L, Vílchez JJ, Márquez C, Bautista J, Guerrero A, Salazar JA, Pou A, Illa I, Gallardo E.

Neuromuscul Disord. 2007 Jan;17(1):69-76. Epub 2006 Oct 27.

PubMed [citation]

PMID:: 17070050

Clinical heterogeneity and a high proportion of novel mutations in a Chinese cohort of patients with dysferlinopathy.

Xi J, Blandin G, Lu J, Luo S, Zhu W, Béroud C, Pécheux C, Labelle V, Lévy N, Urtizberea JA, Zhao C, Krahn M.

Neurol India. 2014 Nov-Dec;62(6):635-9. doi: 10.4103/0028-3886.149386.

PubMed [citation]

PMID:: 25591676

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002283918.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1039 of the DYSF protein (p.Arg1039Gln). This variant is present in population databases (rs149617331, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. ClinVar contains an entry for this variant (Variation ID: 1491619). 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 95%. This variant disrupts the p.Arg1039 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been observed in individuals with DYSF-related conditions (PMID: 17070050, 25591676, 31268554), which suggests that this may be a clinically significant amino acid residue. 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: Sep 29, 2024

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