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NM_005249.5(FOXG1):c.554G>C (p.Ser185Thr) AND Rett syndrome, congenital variant

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 7, 2017
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:
RCV000701355.8

Allele description [Variation Report for NM_005249.5(FOXG1):c.554G>C (p.Ser185Thr)]

NM_005249.5(FOXG1):c.554G>C (p.Ser185Thr)

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.554G>C (p.Ser185Thr)
HGVS:
  • NC_000014.9:g.28767833G>C
  • NG_009367.1:g.5753G>C
  • NM_005249.5:c.554G>CMANE SELECT
  • NP_005240.3:p.Ser185Thr
  • NC_000014.8:g.29237039G>C
  • NM_005249.4:c.554G>C
Protein change:
S185T
Links:
dbSNP: rs1057516138
NCBI 1000 Genomes Browser:
rs1057516138
Molecular consequence:
  • NM_005249.5:c.554G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Rett syndrome, congenital variant
Identifiers:
MedGen: C3150705; Orphanet: 3095; OMIM: 613454

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000830154Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 7, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genomic diagnosis for children with intellectual disability and/or developmental delay.

Bowling KM, Thompson ML, Amaral MD, Finnila CR, Hiatt SM, Engel KL, Cochran JN, Brothers KB, East KM, Gray DE, Kelley WV, Lamb NE, Lose EJ, Rich CA, Simmons S, Whittle JS, Weaver BT, Nesmith AS, Myers RM, Barsh GS, Bebin EM, Cooper GM.

Genome Med. 2017 May 30;9(1):43. doi: 10.1186/s13073-017-0433-1.

PubMed [citation]
PMID:
28554332
PMCID:
PMC5448144

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000830154.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant is not present in population databases (ExAC no frequency). 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. A different missense substitution at this codon (p.Ser185Cys) has been determined to be likely pathogenic (PMID: 28554332). This suggests that the serine residue is critical for FOXG1 protein function and that other missense substitutions at this position may also be pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FOXG1-related disease. This sequence change replaces serine with threonine at codon 185 of the FOXG1 protein (p.Ser185Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine.

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

Last Updated: Feb 25, 2025