NM_130811.4(SNAP25):c.593G>C (p.Arg198Pro) AND Congenital myasthenic syndrome 18

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 2, 2020
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:: RCV001377079.7

Allele description

NM_130811.4(SNAP25):c.593G>C (p.Arg198Pro)

Gene:

SNAP25:synaptosome associated protein 25 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20p12.2

Genomic location:

Preferred name:

NM_130811.4(SNAP25):c.593G>C (p.Arg198Pro)

HGVS:

NC_000020.11:g.10306169G>C
NG_029626.1:g.92341G>C
NM_001322902.2:c.593G>C
NM_001322903.2:c.593G>C
NM_001322904.2:c.593G>C
NM_001322905.2:c.593G>C
NM_001322906.2:c.593G>C
NM_001322907.2:c.593G>C
NM_001322908.2:c.593G>C
NM_001322909.2:c.593G>C
NM_001322910.2:c.593G>C
NM_003081.5:c.593G>C
NM_130811.4:c.593G>CMANE SELECT
NP_001309831.1:p.Arg198Pro
NP_001309832.1:p.Arg198Pro
NP_001309833.1:p.Arg198Pro
NP_001309834.1:p.Arg198Pro
NP_001309835.1:p.Arg198Pro
NP_001309836.1:p.Arg198Pro
NP_001309837.1:p.Arg198Pro
NP_001309838.1:p.Arg198Pro
NP_001309839.1:p.Arg198Pro
NP_003072.2:p.Arg198Pro
NP_570824.1:p.Arg198Pro
NC_000020.10:g.10286817G>C
NM_130811.3:c.593G>C

Protein change:

R198P

Links:

dbSNP: rs2064355563

NCBI 1000 Genomes Browser:

rs2064355563

Molecular consequence:

NM_001322902.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322903.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322904.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322905.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322906.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322907.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322908.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322909.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322910.2:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003081.5:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130811.4:c.593G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital myasthenic syndrome 18
Synonyms:: MYASTHENIC SYNDROME, CONGENITAL, 18, WITH INTELLECTUAL DISABILITY AND ATAXIA
Identifiers:: MONDO: MONDO:0014590; MedGen: C4225364; Orphanet: 590; OMIM: 616330

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001574312	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 2, 2020)	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

SCV001574312

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 2, 2020)

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001574312.4

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

Description

This variant has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 198 of the SNAP25 protein (p.Arg198Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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: Mar 5, 2024

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