Submissions for variant NM_005249.5(FOXG1):c.594C>G (p.Pro198=)

gnomAD frequency: 0.00010  dbSNP: rs141088742

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV004584205	SCV005068286	benign	FOXG1 disorder	2024-04-18	reviewed by expert panel	curation	The allele frequency of the p.Pro198= variant in FOXG1 is 0.04% in African sub population in gnomAD v2.1.1, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Pro198= variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Pro198= variant is found in at least 3 patients with an alternate molecular basis of disease (GeneDx internal database) (BP5_strong). The p.Pro198= variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene; however, as this is a synonymous change, there would be no affect on the amino acid sequence of the functional domain (PM1 not met). In summary, the p.Pro198= variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP5_strong).
GeneDx	RCV000187445	SCV000241037	benign	not specified	2014-08-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000726565	SCV000345561	uncertain significance	not provided	2016-08-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078476	SCV000650055	likely benign	Rett syndrome, congenital variant	2023-12-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354523	SCV002657503	likely benign	Inborn genetic diseases	2020-04-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.