Submissions for variant NM_001349338.3(FOXP1):c.1573C>T (p.Arg525Ter)

dbSNP: rs112795301

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Diagnostic Laboratory, University of Szeged	RCV000005214	SCV000583530	pathogenic	Intellectual disability-severe speech delay-mild dysmorphism syndrome	2017-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000760393	SCV000890265	pathogenic	not provided	2022-03-02	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31785789, 33218123, 25525159, 26647308, 28735298, 30385778, 20950788, 28135719, 30181650)
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000005214	SCV001367889	pathogenic	Intellectual disability-severe speech delay-mild dysmorphism syndrome	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS3,PM4,PM2,PP3. This variant arose de novo in at least one reported proband.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000760393	SCV001447011	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000005214	SCV002557600	pathogenic	Intellectual disability-severe speech delay-mild dysmorphism syndrome	2022-02-02	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with FOXP1-related intellectual disability syndrome (MIM#613670). Dominant negative is also a suggested mechanism of disease. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been well reported as pathogenic, and observed in individuals with FOXP1-related intellectual disability syndrome (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported multiple times as pathogenic, and observed in many individuals with FOXP1-related intellectual disability syndrome, where the variant was proven to be de novo (ClinVar, DECIPHER, PMID: 28735298). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Revvity Omics, Revvity	RCV000005214	SCV003824521	pathogenic	Intellectual disability-severe speech delay-mild dysmorphism syndrome	2022-04-07	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Heidelberg University	RCV000005214	SCV005440679	pathogenic	Intellectual disability-severe speech delay-mild dysmorphism syndrome	2024-07-19	criteria provided, single submitter	clinical testing
OMIM	RCV003761738	SCV000025392	pathogenic	INTELLECTUAL DEVELOPMENTAL DISORDER WITH LANGUAGE IMPAIRMENT AND AUTISTIC FEATURES	2010-11-12	no assertion criteria provided	literature only