Submissions for variant NM_006642.5(SDCCAG8):c.1429G>C (p.Glu477Gln)

gnomAD frequency: 0.00013  dbSNP: rs556191085

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001049051	SCV001213085	uncertain significance	Senior-Loken syndrome 7; Bardet-Biedl syndrome 16	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 477 of the SDCCAG8 protein (p.Glu477Gln). This variant is present in population databases (rs556191085, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 845888). 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 not expected to disrupt SDCCAG8 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.
Genetic Services Laboratory, University of Chicago	RCV001819763	SCV002070284	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	clinical testing	DNA sequence analysis of the SDCCAG8 gene demonstrated a sequence change, c.1429G>C, in exon 12 that results in an amino acid change, p.Glu477Gln. This sequence change has been described in gnomAD with frequency of 0.036% in the African American sub-population (dbSNP rs556191085). The p.Glu477Gln change affects a moderately conserved amino acid residue located in a domain of the SDCCAG8 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Glu477Gln substitution. This sequence change does not appear to have been previously described in patients with SDCCAG8-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Glu477Gln change remains unknown at this time.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294436	SCV002587650	likely benign	Kidney disorder	2017-02-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003413846	SCV004109709	uncertain significance	SDCCAG8-related condition	2024-01-05	criteria provided, single submitter	clinical testing	The SDCCAG8 c.1429G>C variant is predicted to result in the amino acid substitution p.Glu477Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.036% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.