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NM_005249.5(FOXG1):c.259A>C (p.Thr87Pro) AND Rett syndrome, congenital variant

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 29, 2022
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:
RCV002533003.10

Allele description [Variation Report for NM_005249.5(FOXG1):c.259A>C (p.Thr87Pro)]

NM_005249.5(FOXG1):c.259A>C (p.Thr87Pro)

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.259A>C (p.Thr87Pro)
HGVS:
  • NC_000014.9:g.28767538A>C
  • NG_009367.1:g.5458A>C
  • NM_005249.5:c.259A>CMANE SELECT
  • NP_005240.3:p.Thr87Pro
  • NC_000014.8:g.29236744A>C
  • NM_005249.4:c.259A>C
Protein change:
T87P
Links:
dbSNP: rs1566445056
NCBI 1000 Genomes Browser:
rs1566445056
Molecular consequence:
  • NM_005249.5:c.259A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Rett syndrome, congenital variant
Identifiers:
MONDO: MONDO:0013270; 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
SCV003346648Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 29, 2022) 		germlineclinical testing

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

Help

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003346648.2

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

Description

This variant has not been reported in the literature in individuals affected with FOXG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 588146). 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) performed at Invitae indicates that this missense variant is not expected to disrupt FOXG1 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 87 of the FOXG1 protein (p.Thr87Pro).

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

Last Updated: Nov 3, 2024