NM_005055.5(RAPSN):c.264C>A (p.Asn88Lys) AND Congenital myasthenic syndrome 4C

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 17, 2014
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000008512.18

Allele description [Variation Report for NM_005055.5(RAPSN):c.264C>A (p.Asn88Lys)]

NM_005055.5(RAPSN):c.264C>A (p.Asn88Lys)

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.264C>A (p.Asn88Lys)

Other names:

p.N88K

HGVS:

NC_000011.10:g.47448079G>T
NG_008312.1:g.6100C>A
NM_005055.5:c.264C>AMANE SELECT
NM_032645.5:c.264C>A
NP_005046.2:p.Asn88Lys
NP_005046.2:p.Asn88Lys
NP_116034.2:p.Asn88Lys
NC_000011.9:g.47469631G>T
NM_005055.3:c.264C>A
NM_032645.4:c.264C>A
Q13702:p.Asn88Lys

Protein change:

N88K; ASN88LYS

Links:

UniProtKB: Q13702#VAR_021217; OMIM: 601592.0001; dbSNP: rs104894299

NCBI 1000 Genomes Browser:

rs104894299

Molecular consequence:

NM_005055.5:c.264C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032645.5:c.264C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Congenital myasthenic syndrome 4C (CMS4C)
Synonyms:: Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency; Myasthenic syndrome, congenital, postsynaptic, associated with acetylcholine receptor deficiency
Identifiers:: MONDO: MONDO:0012157; MedGen: C1837091; Orphanet: 590; OMIM: 608931

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000221210	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jan 17, 2014)	germline	clinical testing	PubMed (14) [See all records that cite these PMIDs] 14659409, 16945936, 12730725, 12807980, 17190963, 19620612, 20157724, 15482960, 15328566, 11791205, 12796535, 15036330, 21305573, 24033266
SCV001163637	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000221210

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jan 17, 2014)

germline

clinical testing

PubMed (14)
[See all records that cite these PMIDs]

SCV001163637

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nothing to display

See all PubMed Citations (15)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq, SCV000221210.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (14)

Description

The Asn88Lys variant in RAPSN has been previously identified in many individuals with congenital myasthenic syndrome and has been shown to segregate with disease in several affected family members (Ohno 2002, Dunne 2003, Richard 2003, Muller 2003, Banwell 2004, Yasaki 2004, Muller 2004, Ioos 2004, Cossins 2006, Skeie 2006, Milone 2009, Brugoni 2010, Bell 2011, Alseth 2011). This variant has been identified in 0.01% (13/8596) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs104894299). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Functional studies indicate the Asn88Lys variant results in reduced co-localization with the acetylcholine receptor (AChR) (Cossins 2006). In summary, this variant meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LMM) based upon segregation studies and functional evidence.

#	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		1	not provided	1	not provided

From Baylor Genetics, SCV001163637.1

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

Last Updated: Nov 18, 2024

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