Submissions for variant NM_001174150.2(ARL13B):c.599G>A (p.Arg200His)

dbSNP: rs764109067

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001092355	SCV001248816	likely pathogenic	not provided	2019-09-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001859504	SCV002236173	pathogenic	Joubert syndrome 8	2022-10-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg200 amino acid residue in ARL13B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18674751). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARL13B protein function. ClinVar contains an entry for this variant (Variation ID: 266096). This missense change has been observed in individual(s) with Joubert syndrome and related disorders (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 200 of the ARL13B protein (p.Arg200His).
GeneDx	RCV001092355	SCV003924739	likely pathogenic	not provided	2023-05-10	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: 18674751, 27894351, 27457812, 34645488, 34316023)
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000256476	SCV000322790	likely pathogenic	Joubert syndrome and related disorders		no assertion criteria provided	research