Submissions for variant NM_001349338.3(FOXP1):c.1538T>C (p.Val513Ala)

dbSNP: rs1553663140

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000623768	SCV000743031	likely pathogenic	Inborn genetic diseases	2024-09-05	criteria provided, single submitter	clinical testing	The c.1538T>C (p.V513A) alteration is located in exon 18 (coding exon 13) of the FOXP1 gene. This alteration results from a T to C substitution at nucleotide position 1538, causing the valine (V) at amino acid position 513 to be replaced by an alanine (A). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported as heterozygous in multiple individuals with features consistent with FOXP1-related neurodevelopmental disorder; in one individual it was determined to be the result of a de novo mutation (Trelles, 2021; Thorpe, 2024). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.
Illumina Laboratory Services, Illumina	RCV003985092	SCV004801558	uncertain significance	Intellectual disability-severe speech delay-mild dysmorphism syndrome	2018-12-12	criteria provided, single submitter	clinical testing	The FOXP1 c.1538T>C p.(Val513Ala) missense variant has not, to our knowledge, been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 or version 4.0.0 of the Genome Aggregation Database. The variant is located in the FOX domain of the gene. Multiple lines of computational evidence suggest the variant may impact the gene or gene product. Based on the evidence, the c.1538T>C p.(Val513Ala) variant is classified as a variant of uncertain significance for intellectual developmental disorder with language impairment with or without autistic features.
GeneDx	RCV004767449	SCV005377807	pathogenic	not provided	2024-04-18	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26647308, 34588003)