Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478719 | SCV000567914 | uncertain significance | not provided | 2018-03-16 | criteria provided, single submitter | clinical testing | The c.3821_3833del13 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.3821_3833del13 variant is not observed in large population cohorts (Lek et al., 2016). The c.3821_3833del13 variant causes a frameshift starting with codon Serine 1274, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 47 of the new reading frame, denoted p.Ser1274CysfsX47. Although this variant is predicted to cause loss of normal protein function, current evidence indicates that variants in exon 32 are unlikely to cause tuberous sclerosis (Ekong 2016). Specifically, loss-of-function variants in this exon have been identified in the published literature and at GeneDx in individuals who do not have features of TS (Ekong 2016). RNA expression analysis demonstrates an abundance of transcripts lacking this exon in multiple normal tissue types from healthy adults, and in vitro studies indicate that this exon is not essential for normal functional activity of the TSC complex (Ekong 2016). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |