Submissions for variant NM_001329943.3(KIAA0586):c.1080G>C (p.Arg360Ser)

gnomAD frequency: 0.00010  dbSNP: rs200094677

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497904	SCV000590777	uncertain significance	not provided	2017-06-29	criteria provided, single submitter	clinical testing	The R413S variant in the KIAA0586 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R413S variant is not observed in the homozygous state or at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R413S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R413S as a variant of uncertain significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV000660634	SCV000782757	uncertain significance	Joubert syndrome 23	2018-01-11	criteria provided, single submitter	clinical testing
Invitae	RCV001857030	SCV002291948	uncertain significance	Joubert syndrome 23; Short-rib thoracic dysplasia 14 with polydactyly	2022-08-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 413 of the KIAA0586 protein (p.Arg413Ser). This variant is present in population databases (rs200094677, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with KIAA0586-related conditions. ClinVar contains an entry for this variant (Variation ID: 432994). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV003243154	SCV003942547	uncertain significance	Inborn genetic diseases	2023-05-15	criteria provided, single submitter	clinical testing	The c.1080G>C (p.R360S) alteration is located in exon 8 (coding exon 8) of the KIAA0586 gene. This alteration results from a G to C substitution at nucleotide position 1080, causing the arginine (R) at amino acid position 360 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.