NM_001130987.2(DYSF):c.1609G>A (p.Gly537Arg) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 26, 2016
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:: RCV000342783.11

Allele description [Variation Report for NM_001130987.2(DYSF):c.1609G>A (p.Gly537Arg)]

NM_001130987.2(DYSF):c.1609G>A (p.Gly537Arg)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.1609G>A (p.Gly537Arg)

HGVS:

NC_000002.12:g.71551073G>A
NG_008694.1:g.102451G>A
NM_001130455.2:c.1558G>A
NM_001130976.2:c.1513G>A
NM_001130977.2:c.1513G>A
NM_001130978.2:c.1555G>A
NM_001130979.2:c.1648G>A
NM_001130980.2:c.1606G>A
NM_001130981.2:c.1606G>A
NM_001130982.2:c.1651G>A
NM_001130983.2:c.1558G>A
NM_001130984.2:c.1516G>A
NM_001130985.2:c.1609G>A
NM_001130986.2:c.1516G>A
NM_001130987.2:c.1609G>AMANE SELECT
NM_003494.4:c.1555G>A
NP_001123927.1:p.Gly520Arg
NP_001124448.1:p.Gly505Arg
NP_001124449.1:p.Gly505Arg
NP_001124450.1:p.Gly519Arg
NP_001124451.1:p.Gly550Arg
NP_001124452.1:p.Gly536Arg
NP_001124453.1:p.Gly536Arg
NP_001124454.1:p.Gly551Arg
NP_001124455.1:p.Gly520Arg
NP_001124456.1:p.Gly506Arg
NP_001124457.1:p.Gly537Arg
NP_001124458.1:p.Gly506Arg
NP_001124459.1:p.Gly537Arg
NP_003485.1:p.Gly519Arg
LRG_845t1:c.1555G>A
LRG_845t2:c.1609G>A
LRG_845:g.102451G>A
LRG_845p1:p.Gly519Arg
LRG_845p2:p.Gly537Arg
NC_000002.11:g.71778203G>A
NM_003494.3:c.1555G>A
O75923:p.Gly519Arg

Protein change:

G505R; GLY519ARG

Links:

UniProtKB: O75923#VAR_057850; OMIM: 603009.0015; dbSNP: rs121908962

NCBI 1000 Genomes Browser:

rs121908962

Molecular consequence:

NM_001130455.2:c.1558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130976.2:c.1513G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130977.2:c.1513G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130978.2:c.1555G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130979.2:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130980.2:c.1606G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130981.2:c.1606G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130982.2:c.1651G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130983.2:c.1558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130984.2:c.1516G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130985.2:c.1609G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130986.2:c.1516G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130987.2:c.1609G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003494.4:c.1555G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329868	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Sep 26, 2016)	germline	clinical testing	Citation Link,
SCV001244909	Department of Neurology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology	no assertion criteria provided	Pathogenic (Jul 1, 2019)	paternal	reference population	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329868

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Sep 26, 2016)

germline

clinical testing

Citation Link,

SCV001244909

Department of Neurology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology

no assertion criteria provided

Pathogenic
(Jul 1, 2019)

paternal

reference population

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	yes	not provided	not provided	not provided	not provided	not provided	reference population
not provided	germline	yes	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

Identification of splicing defects caused by mutations in the dysferlin gene.

Kergourlay V, Raï G, Blandin G, Salgado D, Béroud C, Lévy N, Krahn M, Bartoli M.

Hum Mutat. 2014 Dec;35(12):1532-41. doi: 10.1002/humu.22710.

PubMed [citation]

PMID:: 25312915

Details of each submission

From GeneDx, SCV000329868.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.1555 G>A pathogenic variant in the DYSF gene has been previously reported in the homozygous state in two siblings with Miyoshi myopathy and absent dysferlin expression on Western blot. Additionally, it was observed in the heterozygous state in their father with calf myalgias and progressive difficulty with walking (Illa et al., 2007). Functional studies demonstrate the c.1555 G>A variant creates a new splice acceptor site resulting in an out-of-frame deletion of 35 base pairs in exon 18 (De Luna et al., 2007; Kergourlay et al., 2014). This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000332008.4

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

#	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		1	not provided	not provided	not provided

From Department of Neurology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, SCV001244909.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	reference population	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000332008	Eurofins Ntd Llc (ga)	flagged submission Reason: Older and outlier claim with insufficient supporting evidence Notes: None (EGL Classification Definitions 2015)	Uncertain significance (Jul 2, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000332008

Eurofins Ntd Llc (ga)

flagged submission

Reason: Older and outlier claim with insufficient supporting evidence

Notes: None

(EGL Classification Definitions 2015)

Uncertain significance
(Jul 2, 2015)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Last Updated: Sep 29, 2024

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