NM_000171.4(GLRA1):c.721C>T (p.Arg241Trp) AND Hereditary hyperekplexia

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 21, 2023
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:: RCV002233641.12

Allele description

NM_000171.4(GLRA1):c.721C>T (p.Arg241Trp)

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.721C>T (p.Arg241Trp)

HGVS:

NC_000005.10:g.151851581G>A
NG_011764.1:g.78256C>T
NM_000171.4:c.721C>TMANE SELECT
NM_001146040.2:c.721C>T
NM_001292000.2:c.472C>T
NP_000162.2:p.Arg241Trp
NP_001139512.1:p.Arg241Trp
NP_001278929.1:p.Arg158Trp
NC_000005.9:g.151231142G>A
NM_000171.3:c.721C>T

Protein change:

R158W

Links:

dbSNP: rs776919102

NCBI 1000 Genomes Browser:

rs776919102

Molecular consequence:

NM_000171.4:c.721C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001146040.2:c.721C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001292000.2:c.472C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary hyperekplexia
Synonyms:: Hyperexplexia, hereditary
Identifiers:: MONDO: MONDO:0021022; MedGen: C1835614; OMIM: PS149400

Recent activity

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Homo sapiens BR serine/threonine kinase 2 (BRSK2), mRNA
Homo sapiens BR serine/threonine kinase 2 (BRSK2), mRNA
gi|27501463|ref|NM_003957.1|

Nucleotide
BR serine/threonine kinase 2 [Homo sapiens]
BR serine/threonine kinase 2 [Homo sapiens]
gi|27501464|ref|NP_003948.1|

Protein
High serum calcifediol
High serum calcifediol

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000826123	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 21, 2023)	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

SCV000826123

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 21, 2023)

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, SCV000826123.3

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 241 of the GLRA1 protein (p.Arg241Trp). This variant is present in population databases (rs776919102, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GLRA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 575323). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GLRA1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 16, 2024

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