NM_000171.4(GLRA1):c.815T>A (p.Ile272Asn) AND Hyperekplexia 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 4, 2012
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:: RCV000017440.30

Allele description [Variation Report for NM_000171.4(GLRA1):c.815T>A (p.Ile272Asn)]

NM_000171.4(GLRA1):c.815T>A (p.Ile272Asn)

Gene:

GLRA1:glycine receptor alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q33.1

Genomic location:

Preferred name:

NM_000171.4(GLRA1):c.815T>A (p.Ile272Asn)

Other names:

I244N

HGVS:

NC_000005.10:g.151851487A>T
NG_011764.1:g.78350T>A
NM_000171.4:c.815T>AMANE SELECT
NM_001146040.2:c.815T>A
NM_001292000.2:c.566T>A
NP_000162.2:p.Ile272Asn
NP_001139512.1:p.Ile272Asn
NP_001278929.1:p.Ile189Asn
NC_000005.9:g.151231048A>T
NM_000171.3:c.815T>A
P23415:p.Ile272Asn

Nucleotide change:

T1112A

Protein change:

I189N; ILE244ASN

Links:

UniProtKB: P23415#VAR_000296; OMIM: 138491.0003; dbSNP: rs121918409

NCBI 1000 Genomes Browser:

rs121918409

Molecular consequence:

NM_000171.4:c.815T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001146040.2:c.815T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001292000.2:c.566T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hyperekplexia 1 (STHE)
Synonyms:: Startle disease, familial; Startle reaction, exaggerated; Stiff-baby syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007868; MedGen: C4551954; Orphanet: 3197; OMIM: 149400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037712	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 1994)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000054505	GeneReviews	no assertion criteria provided	pathologic (Oct 4, 2012)	not provided	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000037712

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 1994)

germline

literature only

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

SCV000054505

GeneReviews

no assertion criteria provided

pathologic
(Oct 4, 2012)

not provided

curation

Help

Summary from all submissions

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

Citations

PubMed

Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor.

Rees MI, Andrew M, Jawad S, Owen MJ.

Hum Mol Genet. 1994 Dec;3(12):2175-9.

PubMed [citation]

PMID:: 7881416

Details of each submission

From OMIM, SCV000037712.3

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

Description

In an apparently sporadic case of startle disease (HKPX1; 149400) in the offspring of a consanguineous marriage, Rees et al. (1994) identified homozygosity for a 1112T-A transversion in the GLRA1 gene, resulting in an ile244-to-asn (I244N) substitution. Both parents and 1 asymptomatic sister were heterozygous for the mutation, which was not found in 300 control chromosomes. The 22-year-old patient was 1 of 6 children in a family described as 'Welsh gypsy of Romany origin' who presented with a long history of recurrent injurious falls. She gave a history of excessive startle and repeated falls in response to sudden, unexpected stimuli. She fell with arms held stiffly by her side and had over the years sustained multiple injuries to body, face, head, and knees. No abnormality was detected on MRI scan. Treated with clonazepam, 4 mg daily, she had no more falls and could walk up and down stairs and outside on her own. The phenotype was indistinguishable from that of dominant hyperekplexia.

#	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 GeneReviews, SCV000054505.2

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

Description

Converted during submission to Pathogenic.

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

Last Updated: Dec 30, 2023

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