NM_005055.5(RAPSN):c.1116GAA[1] (p.Lys373del) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 8, 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:: RCV001050927.7

Allele description [Variation Report for NM_005055.5(RAPSN):c.1116GAA[1] (p.Lys373del)]

NM_005055.5(RAPSN):c.1116GAA[1] (p.Lys373del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_005055.5(RAPSN):c.1116GAA[1] (p.Lys373del)

Other names:

NM_005055.5(RAPSN):c.1116GAA[1]; p.Lys373del

HGVS:

NC_000011.10:g.47438778TCT[1]
NC_000011.10:g.47438778_47438780TCT[1]
NG_008312.1:g.15398GAA[1]
NM_005055.5:c.1116GAA[1]MANE SELECT
NM_032645.5:c.939GAA[1]
NP_005046.2:p.Lys373del
NP_116034.2:p.Lys314del
NC_000011.10:g.47438778TCT[1]
NC_000011.9:g.47460328_47460330del
NC_000011.9:g.47460329TCT[1]
NM_005055.4:c.1119_1121del
NM_005055.4:c.1119_1121delGAA
NM_005055.5:c.1119_1121delMANE SELECT

Protein change:

K314del

Links:

dbSNP: rs759488854

NCBI 1000 Genomes Browser:

rs759488854

Molecular consequence:

NM_005055.5:c.1116GAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_032645.5:c.939GAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Fetal akinesia deformation sequence 1 (FADS1)
Synonyms:: Pena Shokeir syndrome, type 1; Lethal Pena-Shokeir 1 syndrome; Pena-Shokeir syndrome type I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100101; MedGen: C1276035; Orphanet: 994; OMIM: 208150; Human Phenotype Ontology: HP:0001989

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

Recent activity

Clear Turn Off Turn On

Chromosome neighbors for GEO Profiles (Select 5614556) (20)
GEO Profiles
Homo sapiens full open reading frame cDNA clone RZPDo834A0836D for gene PPT1, pa...
Homo sapiens full open reading frame cDNA clone RZPDo834A0836D for gene PPT1, palmitoyl-protein thioesterase 1 (ceroid-lipofuscinosis, neuronal 1, infantile); complete cds, without stopcodon
gi|49457058|emb|CR542053.1|

Nucleotide
menin isoform X1 [Homo sapiens]
menin isoform X1 [Homo sapiens]
gi|1034573762|ref|XP_016873257.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001215057	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 8, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19620612, 16945936, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001215057

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 8, 2024)

germline

clinical testing

PubMed (3)
[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

Myasthenic syndrome due to defects in rapsyn: Clinical and molecular findings in 39 patients.

Milone M, Shen XM, Selcen D, Ohno K, Brengman J, Iannaccone ST, Harper CM, Engel AG.

Neurology. 2009 Jul 21;73(3):228-35. doi: 10.1212/WNL.0b013e3181ae7cbc.

PubMed [citation]

PMID:: 19620612
PMCID:: PMC2715575

Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations.

Cossins J, Burke G, Maxwell S, Spearman H, Man S, Kuks J, Vincent A, Palace J, Fuhrer C, Beeson D.

Brain. 2006 Oct;129(Pt 10):2773-83. Epub 2006 Aug 31.

PubMed [citation]

PMID:: 16945936

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001215057.5

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

Description

This variant, c.1119_1121del, results in the deletion of 1 amino acid(s) of the RAPSN protein (p.Lys373del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs759488854, gnomAD 0.001%). This variant has been observed in individuals with congenital myasthenic syndrome (CMS) (PMID: 16945936, 19620612; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 847394). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects RAPSN function (PMID: 16945936). For these reasons, this variant has been classified as 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: Jun 2, 2024

ClinVar

Relating variation to medicine