Submissions for variant NM_003042.4(SLC6A1):c.631C>T (p.Arg211Cys)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005058246	SCV002595668	uncertain significance	Epilepsy with myoclonic atonic seizures	2023-07-30	criteria provided, single submitter	clinical testing	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 SLC6A1 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. ClinVar contains an entry for this variant (Variation ID: 1714623). This variant has not been reported in the literature in individuals affected with SLC6A1-related conditions. This variant is present in population databases (rs756927822, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 211 of the SLC6A1 protein (p.Arg211Cys).
GeneDx	RCV003328695	SCV004035886	uncertain significance	not provided	2023-03-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign in association with a SLC6A1-related disorder to our knowledge; This variant is associated with the following publications: (PMID: Trinidad2022[FunctionalStudy], 31932766)
CeGaT Center for Human Genetics Tuebingen	RCV003328695	SCV005434176	uncertain significance	not provided	2024-09-01	criteria provided, single submitter	clinical testing