Submissions for variant NM_001349338.3(FOXP1):c.1241del (p.Leu414fs)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002471982	SCV002767683	pathogenic	Intellectual disability-severe speech delay-mild dysmorphism syndrome	2020-05-25	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 15 of 21). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Multiple variants predicted to result in NMD have been reported pathogenic (ClinVar, Decipher). (P) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Labcorp Genetics (formerly Invitae), Labcorp	RCV002571475	SCV003473133	pathogenic	not provided	2024-09-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu414Argfs*60) in the FOXP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FOXP1 are known to be pathogenic (PMID: 28735298). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with FOXP1-related conditions (PMID: 30564305, 34109629). ClinVar contains an entry for this variant (Variation ID: 1805564). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV002571475	SCV005327589	pathogenic	not provided	2023-10-19	criteria provided, single submitter	clinical testing	Frameshift 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34109629, 30564305)
PreventionGenetics, part of Exact Sciences	RCV003943412	SCV004759334	pathogenic	FOXP1-related disorder	2023-12-18	no assertion criteria provided	clinical testing	The FOXP1 c.1241delT variant is predicted to result in a frameshift and premature protein termination (p.Leu414Argfs*60). This variant was reported as de novo variant in two individuals with autism spectrum disorder (Guo et al 2018. PubMed ID: 30564305; Braden et al 2021. PubMed ID: 34109629). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in FOXP1 are expected to be pathogenic. This variant is interpreted as pathogenic.