U.S. flag

An official website of the United States government

NM_177402.5(SYT2):c.1112T>A (p.Ile371Lys) AND Congenital myasthenic syndrome 7

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 6, 2021
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:
RCV001553803.1

Allele description [Variation Report for NM_177402.5(SYT2):c.1112T>A (p.Ile371Lys)]

NM_177402.5(SYT2):c.1112T>A (p.Ile371Lys)

Gene:
SYT2:synaptotagmin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_177402.5(SYT2):c.1112T>A (p.Ile371Lys)
Other names:
I371K
HGVS:
  • NC_000001.11:g.202596905A>T
  • NG_041776.1:g.118519T>A
  • NM_001136504.1:c.1112T>A
  • NM_177402.5:c.1112T>AMANE SELECT
  • NP_001129976.1:p.Ile371Lys
  • NP_796376.2:p.Ile371Lys
  • NC_000001.10:g.202566033A>T
Protein change:
ILE371LYS
Links:
OMIM: 600104.0003; dbSNP: rs1690318147
NCBI 1000 Genomes Browser:
rs1690318147
Molecular consequence:
  • NM_001136504.1:c.1112T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_177402.5:c.1112T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital myasthenic syndrome 7
Synonyms:
Myasthenic syndrome, congenital, 7, presynaptic; MYASTHENIC SYNDROME, CONGENITAL, 7A, PRESYNAPTIC, AND DISTAL MOTOR NEUROPATHY, AUTOSOMAL DOMINANT
Identifiers:
MONDO: MONDO:0014468; MedGen: C4015038; Orphanet: 590; OMIM: 616040

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001774823OMIM
no assertion criteria provided
Pathogenic
(Aug 6, 2021) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Identification of a new SYT2 variant validates an unusual distal motor neuropathy phenotype.

Montes-Chinea NI, Guan Z, Coutts M, Vidal C, Courel S, Rebelo AP, Abreu L, Zuchner S, Littleton JT, Saporta MA.

Neurol Genet. 2018 Dec;4(6):e282. doi: 10.1212/NXG.0000000000000282.

PubMed [citation]
PMID:
30533528
PMCID:
PMC6244021

Details of each submission

From OMIM, SCV001774823.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 50-year-old woman and her similarly affected mother with presynaptic congenital myasthenic syndrome-7A and distal motor neuropathy (CMS7A; 616040), Montes-Chinea et al. (2018) identified a heterozygous c.1112T-A transversion in the SYT2 gene, resulting in an ile371-to-lys (I371K) substitution at a conserved residue in the C2B domain. The mutation, which was found by Sanger sequencing, was not present in the gnomAD database. Family history revealed several other similarly affected family members, but they were not studied. Expression of the orthologous mutation in the Drosophila homolog (dsyt1) was unable to rescue reduced viability in dsyt1-null flies, caused an additional decrease in viability compared to complete gene loss, and resulted in defects in calcium-triggered synaptic transmission, all in a dominant-negative manner. The patients had clear clinical and electrophysiologic evidence of both impaired presynaptic neuromuscular transmission and a distal motor neuropathy.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2023