ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.271C>A (p.Pro91Thr)

gnomAD frequency: 0.00002  dbSNP: rs1555321245
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542747 SCV000650048 uncertain significance Rett syndrome, congenital variant 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 91 of the FOXG1 protein (p.Pro91Thr). This variant is not present in population databases (gnomAD no frequency). 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: 471468). 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.
Baylor Genetics RCV000542747 SCV001524957 uncertain significance Rett syndrome, congenital variant 2019-03-27 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000542747 SCV002495781 uncertain significance Rett syndrome, congenital variant 2022-02-03 criteria provided, single submitter clinical testing FOXG1 NM_005249.4 exon 1 p.Pro91Thr (c.271C>A): This variant has not been reported in the literature but is present in 0.004% (2/4100) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-28767550-C-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:471468). Evolutionary conservation for this variant is limited or unavailable; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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