Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000767144 | SCV000516726 | uncertain significance | not provided | 2017-09-14 | criteria provided, single submitter | clinical testing | The G630D variant has not been published as a pathogenic variant, nor has it been reported as abenign variant to our knowledge. The G630D variant is not observed in large population cohorts (Leket al., 2016). The G630D variant is a non-conservative amino acid substitution, which is likely toimpact secondary protein structure as these residues differ in polarity, charge, size and/or otherproperties. This substitution occurs at a position that is conserved across species, and in silico analysispredicts this variant is probably damaging to the protein structure/function. In summary, based on thecurrently available information, it is unclear whether this variant is a pathogenic variant or a rarebenign variant. |
ARUP Laboratories, |
RCV000444052 | SCV000605470 | uncertain significance | not specified | 2017-03-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000546851 | SCV000644294 | uncertain significance | Tuberous sclerosis 2 | 2017-06-08 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on TSC2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a TSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 379559). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 630 of the TSC2 protein (p.Gly630Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |
Genome- |
RCV000546851 | SCV002040647 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002411311 | SCV002719403 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-06 | criteria provided, single submitter | clinical testing | The p.G630D variant (also known as c.1889G>A), located in coding exon 17 of the TSC2 gene, results from a G to A substitution at nucleotide position 1889. The glycine at codon 630 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with TSC2-related disease (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |