Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002381327 | SCV002694139 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-08-03 | criteria provided, single submitter | clinical testing | The p.L320F variant (also known as c.960G>T), located in coding exon 9 of the TSC2 gene, results from a G to T substitution at nucleotide position 960. The leucine at codon 320 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was detected in an individual with a clinical diagnosis of tuberous sclerosis complex (TSC); however authors referred to the alteration as p.F320L (c.978T>G) (Zhang H et al. J. Hum. Genet., 1999;44:391-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003626599 | SCV004465068 | uncertain significance | Tuberous sclerosis 2 | 2023-05-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 320 of the TSC2 protein (p.Leu320Phe). This variant is not present in population databases (gnomAD no frequency). 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 not expected to disrupt TSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 49408). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. |
| Tuberous sclerosis database |
RCV000042668 | SCV000066463 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |