NM_005249.5(FOXG1):c.670G>A (p.Gly224Ser) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Dec 13, 2016)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000153265.3

Allele description [Variation Report for NM_005249.5(FOXG1):c.670G>A (p.Gly224Ser)]

NM_005249.5(FOXG1):c.670G>A (p.Gly224Ser)

Gene:
FOXG1:forkhead box G1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q12
Genomic location:
Preferred name:
NM_005249.5(FOXG1):c.670G>A (p.Gly224Ser)
HGVS:
  • NC_000014.9:g.28767949G>A
  • NG_009367.1:g.5869G>A
  • NM_005249.5:c.670G>AMANE SELECT
  • NP_005240.3:p.Gly224Ser
  • NP_005240.3:p.Gly224Ser
  • NC_000014.8:g.29237155G>A
  • NM_005249.3:c.670G>A
  • NM_005249.4:c.670G>A
Protein change:
G224S
Links:
dbSNP: rs727503935
NCBI 1000 Genomes Browser:
rs727503935
Molecular consequence:
  • NM_005249.5:c.670G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000202741EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Likely pathogenic
(Apr 9, 2014)
germlineclinical testing

Citation Link,

SCV000492334GeneDxcriteria provided, single submitter
Likely pathogenic
(Dec 13, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000202741.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000492334.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

A G224S variant that is likely pathogenic has been identified in the FOXG1 gene. The G224S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G224S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G224S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, the G224S variant occurs within the forkhead binding domain where all previously reported missense variants in FOXG1 have been identified and multiple missense variants in nearby residues have been reported in Human Gene Mutation Database in association with FOXG1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Sep 18, 2021

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