Submissions for variant NM_022370.4(ROBO3):c.1379A>G (p.Gln460Arg)

gnomAD frequency: 0.00002  dbSNP: rs771613910

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000779048	SCV000915508	uncertain significance	Gaze palsy, familial horizontal, with progressive scoliosis 1	2018-12-17	criteria provided, single submitter	clinical testing	The ROBO3 c.1379A>G (p.Gln460Arg) missense variant has been reported in one study in which it is identified in two siblings with familial horizontal gaze palsy with progressive scoliosis in a homozygous state (Abu-Amero et al. 2009). The parents and unaffected brother of the sisters were heterozygous for the variant. The p.Gln460Arg variant was absent from 170 healthy controls and is reported at a frequency of 0.000016 in the total population of the Genome Aggregation Database. Based on the evidence, the p.Gln460Arg variant is classified as a variant of unknown significance but suspicious for pathogenicity for familial horizontal gaze palsy with progressive scoliosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000779048	SCV001468598	likely pathogenic	Gaze palsy, familial horizontal, with progressive scoliosis 1	2021-01-09	criteria provided, single submitter	curation	This ROBO3 variant was reported as Pathogenic​ in PMID: 18829051 with original nomenclature reported as c.1379A>G, Q460R. Variant was re-classified as Likely Pathogenic based on the criteria PM2_Supporting, PM3_Moderate, PP3_Supporting, PP4_Supporting.