Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000814702 | SCV000955122 | uncertain significance | Tuberous sclerosis 2 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 954 of the TSC2 protein (p.Lys954Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autism spectrum disorder (ASD) (PMID: 23514105). ClinVar contains an entry for this variant (Variation ID: 65263). 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 TSC2 protein function with a negative predictive value of 95%. 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 | RCV002433552 | SCV002745871 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-02 | criteria provided, single submitter | clinical testing | The p.K954R variant (also known as c.2861A>G), located in coding exon 25 of the TSC2 gene, results from an A to G substitution at nucleotide position 2861. The lysine at codon 954 is replaced by arginine, an amino acid with highly similar properties. This variant was reported in a cohort of patients with an autism spectrum disorder (Bahl S et al. Mol Autism, 2013 Mar;4:5). This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998182 | SCV005622684 | uncertain significance | not provided | 2024-06-26 | criteria provided, single submitter | clinical testing | |
| Tuberous sclerosis database |
RCV000055484 | SCV000083706 | not provided | Autism spectrum disorder | no assertion provided | curation |