Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Clinical Genetics, |
RCV002226880 | SCV002505773 | likely pathogenic | Tuberous sclerosis 2 | 2021-08-01 | criteria provided, single submitter | clinical testing | |
New York Genome Center | RCV002226880 | SCV002564272 | uncertain significance | Tuberous sclerosis 2 | 2022-02-23 | criteria provided, single submitter | clinical testing | The mosaic c.1257+5G>A variant in TSC2 has not previously been reported in the literature or public variant repositories (ClinVar and LOVD), and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.1257+5G>A variant was detected at ~10% mosaicism level (4/39 reads) in this individual. The c.1257+5G>A variant is located in the splice region after exon 12of this 41-exon gene, and is predicted to result in loss of native splice donor site (splice AI donor loss= 0.89) and activate a new splice donor site 12 nucleotides downstream of the variant (splice AI donor gain = 0.61); however, there are no functional studies to support or refute these predictions. Based on available evidence this mosaic heterozygous c.1257+5G>A variant in TSC2 identified is classified as a Variant of Uncertain Significance. |