Submissions for variant NM_006642.5(SDCCAG8):c.1892C>T (p.Thr631Ile)

gnomAD frequency: 0.00003  dbSNP: rs565662622

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002020389	SCV002296396	uncertain significance	Senior-Loken syndrome 7; Bardet-Biedl syndrome 16	2023-04-27	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1505153). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is present in population databases (rs565662622, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 631 of the SDCCAG8 protein (p.Thr631Ile). 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.
PreventionGenetics, part of Exact Sciences	RCV004529086	SCV004110365	uncertain significance	SDCCAG8-related disorder	2022-11-04	criteria provided, single submitter	clinical testing	The SDCCAG8 c.1892C>T variant is predicted to result in the amino acid substitution p.Thr631Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-243589767-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.