Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001026014 | SCV001188314 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-09-26 | criteria provided, single submitter | clinical testing | The p.L236P variant (also known as c.707T>C), located in coding exon 7 of the TSC2 gene, results from a T to C substitution at nucleotide position 707. The leucine at codon 236 is replaced by proline, an amino acid with similar properties. This alteration has been detected multiple individuals meeting a definite diagnosis for tuberous sclerosis and the variant segregated with disease in these families (Ambry internal data; Fokkema IF et al. Hum. Mutat. 2011 May;32:557-63). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Invitae | RCV001862350 | SCV002304380 | uncertain significance | Tuberous sclerosis 2 | 2021-02-14 | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 826824). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 236 of the TSC2 protein (p.Leu236Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |