Submissions for variant NM_000368.5(TSC1):c.515dup (p.Ala173fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526557	SCV005040548	pathogenic	Tuberous sclerosis syndrome	2024-03-01	criteria provided, single submitter	clinical testing	Variant summary: TSC1 c.515dupT (p.Ala173GlyfsX45) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251390 control chromosomes (gnomAD). To our knowledge, no occurrence of c.515dupT in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005100807	SCV005830644	pathogenic	Tuberous sclerosis 1	2024-09-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala173Glyfs*45) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. For these reasons, this variant has been classified as Pathogenic.