NM_001127644.2(GABRA1):c.799C>A (p.Leu267Ile) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Nov 5, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000816542.1

Allele description [Variation Report for NM_001127644.2(GABRA1):c.799C>A (p.Leu267Ile)]

NM_001127644.2(GABRA1):c.799C>A (p.Leu267Ile)

Gene:
GABRA1:gamma-aminobutyric acid type A receptor subunit alpha1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q34
Genomic location:
Preferred name:
NM_001127644.2(GABRA1):c.799C>A (p.Leu267Ile)
Other names:
p.L267I:CTC>ATC
HGVS:
  • NC_000005.10:g.161890993C>A
  • NG_011548.1:g.48803C>A
  • NM_000806.5:c.799C>A
  • NM_001127643.2:c.799C>A
  • NM_001127644.2:c.799C>AMANE SELECT
  • NM_001127645.2:c.799C>A
  • NM_001127648.2:c.799C>A
  • NP_000797.2:p.Leu267Ile
  • NP_001121115.1:p.Leu267Ile
  • NP_001121116.1:p.Leu267Ile
  • NP_001121117.1:p.Leu267Ile
  • NP_001121120.1:p.Leu267Ile
  • NC_000005.9:g.161317999C>A
Protein change:
L267I
Links:
dbSNP: rs796052492
NCBI 1000 Genomes Browser:
rs796052492
Molecular consequence:
  • NM_000806.5:c.799C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127643.2:c.799C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127644.2:c.799C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127645.2:c.799C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127648.2:c.799C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Idiopathic generalized epilepsy
Synonyms:
EIG; Generalised epilepsy
Identifiers:
MONDO: MONDO:0005579; MedGen: C0270850; OMIM: 600669; OMIM: PS600669
Name:
Epilepsy, juvenile myoclonic 5 (EIG13)
Synonyms:
EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 5; EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 13
Identifiers:
MONDO: MONDO:0012627; MedGen: C4013473; Orphanet: 307; Orphanet: 64280; OMIM: 611136
Name:
Epilepsy, childhood absence 4 (ECA4)
Synonyms:
EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 4
Identifiers:
MedGen: C1970160; Orphanet: 307

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000957057Invitaecriteria provided, single submitter
Uncertain significance
(Nov 5, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000957057.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces leucine with isoleucine at codon 267 of the GABRA1 protein (p.Leu267Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GABRA1-related disease. ClinVar contains an entry for this variant (Variation ID: 205521). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Mar 7, 2021

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