Submissions for variant NM_006516.4(SLC2A1):c.631C>T (p.Pro211Ser)

dbSNP: rs796053247

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189354	SCV000242990	likely pathogenic	not provided	2013-07-10	criteria provided, single submitter	clinical testing	p.Pro211Ser (CCC>TCC): c.631 C>T in the SLC2A1 gene (NM_006516.2). The P211S missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. P211S is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. The variant occurs at a highly conserved position in in the cytoplasmic loop between the sixth and seventh transmembrane segments of the SLC2A1 protein. Multiple published missense mutations have been reported in this same region of the protein, supporting the functional importance of this region of the protein. Additionally, multiple in silico algorithms predict that P211S may be damaging to protein structure/function. However, the possibility that it is a benign variant cannot be completely excluded. The variant is found in CHILD-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001365001	SCV001561217	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2020-11-19	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 expected to disrupt SLC2A1 protein function. This variant has been observed in individual(s) with epilepsy and/or neurodevelopmental disorders (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 207192). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 211 of the SLC2A1 protein (p.Pro211Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine.