Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001071260 | SCV001236554 | uncertain significance | Tuberous sclerosis 1 | 2019-03-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TSC1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 1130 of the TSC1 protein (p.Lys1130Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Ambry Genetics | RCV002451311 | SCV002617205 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-16 | criteria provided, single submitter | clinical testing | The p.K1130N variant (also known as c.3390G>C), located in coding exon 21 of the TSC1 gene, results from a G to C substitution at nucleotide position 3390. The lysine at codon 1130 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |