Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000803397 | SCV000943266 | benign | Tuberous sclerosis 2 | 2024-01-19 | criteria provided, single submitter | clinical testing | |
St. |
RCV001526823 | SCV001737478 | uncertain significance | Tuberous sclerosis syndrome | 2021-05-27 | criteria provided, single submitter | clinical testing | The TSC2 c.1928A>G (p.Tyr643Cys) missense change has a maximum subpopulation frequency of 0.0040% in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/variant/16-2121599-A-G?dataset=gnomad_r2_1). Seven of seven in silico tools predict a deleterious effect of this variant on protein function (PP3), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with tuberous sclerosis complex. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_Supporting, PP3. |
Gene |
RCV001592994 | SCV001817357 | uncertain significance | not provided | 2022-07-20 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Observed in 0.0007% (2/281658 alleles) in large population cohorts (gnomAD) |
Genome- |
RCV000803397 | SCV002040651 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002406784 | SCV002719854 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-20 | criteria provided, single submitter | clinical testing | The p.Y643C variant (also known as c.1928A>G), located in coding exon 17 of the TSC2 gene, results from an A to G substitution at nucleotide position 1928. The tyrosine at codon 643 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002501080 | SCV002786692 | uncertain significance | Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 | 2022-03-14 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003396403 | SCV004111966 | uncertain significance | TSC2-related condition | 2023-02-25 | criteria provided, single submitter | clinical testing | The TSC2 c.1928A>G variant is predicted to result in the amino acid substitution p.Tyr643Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2121599-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |