Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001342211 | SCV001536127 | uncertain significance | Tuberous sclerosis 2 | 2020-09-03 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this variant affects TSC2 protein function (PMID: 22903760). This variant has been observed in individual(s) with tuberous sclerosis complex (PMID: 22903760). ClinVar contains an entry for this variant (Variation ID: 65153). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with phenylalanine at codon 1673 of the TSC2 protein (p.Val1673Phe). The valine residue is weakly conserved and there is a small physicochemical difference between valine and phenylalanine. |
| Ambry Genetics | RCV002336203 | SCV002640836 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-30 | criteria provided, single submitter | clinical testing | The p.V1673F variant (also known as c.5017G>T), located in coding exon 38 of the TSC2 gene, results from a G to T substitution at nucleotide position 5017. The valine at codon 1673 is replaced by phenylalanine, an amino acid with highly similar properties. In one functional study, this alteration was found to disrupt the TSC1-TSC2 dependent inhibition of TORC1 (Hoogeveen-Westerveld M et al. Hum Mutat, 2013 Jan;34:167-75). In addition, this alteration has been observed in at least one individual with a personal history that is consistent with TSC-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Tuberous sclerosis database |
RCV000055369 | SCV000083590 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |