ClinVar Miner

Submissions for variant NM_006642.5(SDCCAG8):c.1513C>G (p.Gln505Glu)

gnomAD frequency: 0.00007  dbSNP: rs980791573
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001039799 SCV001203346 uncertain significance Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 2022-10-04 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 838283). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 505 of the SDCCAG8 protein (p.Gln505Glu).
Genetic Services Laboratory, University of Chicago RCV001819747 SCV002064830 uncertain significance not specified 2020-10-23 criteria provided, single submitter clinical testing DNA sequence analysis of the SDCCAG8 gene demonstrated a sequence change, c.1513C>G, in exon 13 that results in an amino acid change, p.Gln505Glu. This sequence change does not appear to have been previously described in patients with SDCCAG8-related disorders and has been described in the gnomAD database with a frequency of 0.024% in the African sub-population (dbSNP rs980791573). The p.Gln505Glu change affects a highly 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.Gln505Glu substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Gln505Glu change remains unknown at this time.
Fulgent Genetics, Fulgent Genetics RCV001039799 SCV002777230 uncertain significance Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 2021-08-05 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004536073 SCV004119832 uncertain significance SDCCAG8-related disorder 2023-11-21 criteria provided, single submitter clinical testing The SDCCAG8 c.1513C>G variant is predicted to result in the amino acid substitution p.Gln505Glu. This variant has been reported in the heterozygous state in an individual with Bardet-Biedl syndrome; however, this individual also carried a homozygous nonsense variant in BBS2 which provided the diagnosis (Redin et al. 2012. PubMed ID: 22773737). This variant is reported in 0.024% 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 RCV004691317 SCV005186402 uncertain significance not provided criteria provided, single submitter not provided

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