Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001915180 | SCV002168076 | uncertain significance | not provided | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with alanine at codon 1302 of the SI protein (p.Gly1302Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs780497188, ExAC 0.07%). This variant has not been reported in the literature in individuals with SI-related conditions. 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 SI 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. |
Neuberg Centre For Genomic Medicine, |
RCV003339799 | SCV004047675 | uncertain significance | Sucrase-isomaltase deficiency | criteria provided, single submitter | clinical testing | The missense variant c.3905G>C (p.Gly1302Ala) has been submitted to ClinVar as a Variant of Uncertain Significance (VUS), but no details are available for independent assessment. It has not been reported in affected individuals. This p.Gly1302Ala variant has allele frequency of 0.0080% in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Gly at position 1302 is changed to a Ala changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Gly1302Ala in SI is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS). |