Submissions for variant NM_000548.5(TSC2):c.5289del (p.Ser1764fs)

dbSNP: rs1555441221

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627448	SCV000748448	pathogenic	not provided	2018-03-13	criteria provided, single submitter	clinical testing	The c.5289delC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant causes a frameshift starting with codon Serine 1764, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 62 of the new reading frame, denoted p.Ser1764AlafsX62. This variant is predicted to cause a proteinextension as the last 44 amino acids are replaced with 61 incorrect amino acids. Additionally, other frameshift variants downstream of this position have been reported in the TSC2 gene in association with tuberous sclerosis complex (Stenson et al., 2014). Furthermore, the c.5289delC variant is not observed in largepopulation cohorts (Lek et al., 2016). Therefore, the c.5289delCvariant is interpreted to be a pathogenic variant.
Athena Diagnostics Inc	RCV000627448	SCV001146289	pathogenic	not provided	2019-06-28	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Genome-Nilou Lab	RCV001797767	SCV002041033	pathogenic	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing