Submissions for variant NM_001378974.1(FBXW11):c.856T>C (p.Trp286Arg)

dbSNP: rs1758225061

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001095749	SCV001251592	likely pathogenic	FBXW11-related neurodevelopmental, brain, eye, and digit anomalies	2021-03-25	criteria provided, single submitter	clinical testing	The FBXW11 c.793T>C (p.Trp265Arg) variant is a missense variant. A literature search was conducted for the gene, cDNA change, and amino acid change. No publications were identified through this search. The p.Trp265Arg variant is not found in the Genome Aggregation Database in a region of good sequencing coverage. It is therefore presumed to be rare. This variant is located in the first of seven WD40 domains, which are believed to be important for secondary protein structure and protein-protein interactions. In silico tools also consistently predict this variant to have a deleterious effect, but these predictions have not been assessed experimentally. The variant segregates with disease in three similarly affected individuals from one family, which includes this individual. Based on the application of ACMG criteria, the p.Trp265Arg variant is classified as likely pathogenic for FBXW11-related neurodevelopmental, brain, eye, and digit anomalies.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV002468623	SCV002764696	likely pathogenic	Neurodevelopmental, jaw, eye, and digital syndrome	2021-09-13	criteria provided, single submitter	clinical testing
GeneDx	RCV003106110	SCV003761576	uncertain significance	not provided	2022-07-30	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; Has not been previously published as pathogenic or benign to our knowledge
Institute of Human Genetics, University of Leipzig Medical Center	RCV002468623	SCV004698119	likely pathogenic	Neurodevelopmental, jaw, eye, and digital syndrome	2024-02-22	criteria provided, single submitter	clinical testing	Criteria applied: PS2_MOD,PS4_SUP,PM2_SUP,PP2,PP3
CeGaT Center for Human Genetics Tuebingen	RCV003106110	SCV005041078	likely pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	FBXW11: PM2, PP2, PP3, PS2:Supporting, PS4:Supporting
Suzhou Clinical Center for Rare Diseases in Children, Children's Hospital of Soochow University	RCV002468623	SCV005373505	likely pathogenic	Neurodevelopmental, jaw, eye, and digital syndrome	2024-09-01	criteria provided, single submitter	clinical testing	The NM_012300.2:c.793T>C (p.Trp286Arg) variant of FBXW11 is a missense mutation that was not detected in the peripheral blood of the subject's parents, suggesting it may be a de novo mutation (PS2). This variant has not been recorded in the gnomAD database (v4.1.0) (PM2_Supproting).Revel score is 0.93 (PP3_Morderate). According to the ACMG guidelines, this mutation is interpreted as likely pathogenic (PS2+PM2_Supproting+PP3_Morderate).