NM_005055.5(RAPSN):c.-210A>G AND Congenital myasthenic syndrome 11

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 2, 2020
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000008517.7

Allele description [Variation Report for NM_005055.5(RAPSN):c.-210A>G]

NM_005055.5(RAPSN):c.-210A>G

Gene:

RAPSN:receptor associated protein of the synapse [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_005055.5(RAPSN):c.-210A>G

Other names:

-38A>G

HGVS:

NC_000011.10:g.47449174T>C
NG_008312.2:g.4962A>G
NM_005055.5:c.-210A>GMANE SELECT
NC_000011.9:g.47470726T>C
NG_008312.1:g.5005A>G
NM_005055.4:c.-210A>G

Note:

NCBI staff reviewed the sequence information reported in PubMed 12651869 Fig. 4B to determine the location of this allele on the current reference sequence.

Nucleotide change:

-38A-G

Links:

OMIM: 601592.0006; dbSNP: rs786200905

NCBI 1000 Genomes Browser:

rs786200905

Condition(s)

Name:: Congenital myasthenic syndrome 11
Synonyms:: MYASTHENIC SYNDROME, CONGENITAL, Ie; Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency
Identifiers:: MONDO: MONDO:0014588; MedGen: C4225367; Orphanet: 590; OMIM: 616326

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ALDH5A1 [Talpa occidentalis]
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028725	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2004)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 12651869, 2245297, 15282317
SCV001437503	Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences	no assertion criteria provided	Likely pathogenic (Sep 2, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028725

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2004)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

SCV001437503

Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences

no assertion criteria provided

Likely pathogenic
(Sep 2, 2020)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome.

Ohno K, Sadeh M, Blatt I, Brengman JM, Engel AG.

Hum Mol Genet. 2003 Apr 1;12(7):739-48.

PubMed [citation]

PMID:: 12651869

Congenital myasthenia associated with facial malformations in Iraqi and Iranian Jews. A new genetic syndrome.

Goldhammer Y, Blatt I, Sadeh M, Goodman RM.

Brain. 1990 Oct;113 ( Pt 5):1291-306.

PubMed [citation]

PMID:: 2245297

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000028725.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In 6 patients with congenital myasthenic syndrome-11 (CMS11; 616326) associated with AChR deficiency and facial dysmorphism, Ohno et al. (2003) identified a homozygous -38A-G transition in the promoter region of the RAPSN gene. All patients were of either Iraqi or Iranian origin and were first reported by Goldhammer et al. (1990). Haplotype analysis showed a founder effect for the mutation. Functional expression studies suggested that the -38G-A mutation impaired transcription, leading to reduced RAPSN expression, and endplate AChR deficiency.

Rodova et al. (2004) showed that site-specific mutation of the RAPSYN promoter to produce the -38A-G mutation resulted in reduced muscle-specific activation of the promoter by mouse Kaiso (ZBTB33; 300329) and Ctnnd2 (604275).

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

From Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences, SCV001437503.1

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

Description

Onset at age 6 years with poor feeding, weak cry, ptosis, facial weakness and long face, high arched palate. Slow RNS was in favor of a neuromuscular junction disorder.

#	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

Last Updated: Sep 29, 2024

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