ClinVar Miner

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

gnomAD frequency: 0.00013  dbSNP: rs556191085
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Total submissions: 5
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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 RCV004528356 SCV004109709 uncertain significance SDCCAG8-related disorder 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.
Breakthrough Genomics, Breakthrough Genomics RCV004691320 SCV005186401 uncertain significance not provided criteria provided, single submitter not provided

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