ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.826_827del (p.Met276fs) (rs137853977)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000312270 SCV000232977 pathogenic not provided 2015-01-09 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000180518 SCV000255920 pathogenic Tuberous sclerosis 2 2014-09-24 criteria provided, single submitter clinical testing
GeneDx RCV000312270 SCV000329784 pathogenic not provided 2018-10-03 criteria provided, single submitter clinical testing The c.826_827delAT pathogenic variant in the TSC2 gene has been reported multiple times previously in association with tuberous sclerosis complex (Niida et al., 1999; TSC2 LOVD). The deletion causes a frameshift starting with codon Methionine 276, changes this amino acid to a Valine residue and creates a premature Stop codon at position 61 of the new reading frame, denoted p.Met276ValfsX61. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally, it was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we consider c.826_827delAT to be a pathogenic variant.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000180518 SCV000782396 pathogenic Tuberous sclerosis 2 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000180518 SCV001220719 pathogenic Tuberous sclerosis 2 2019-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met276Valfs*61) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with tuberous sclerosis complex (PMID: 10533067, 11112665, 16114042). ClinVar contains an entry for this variant (Variation ID: 49447). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042707 SCV000066502 not provided Tuberous sclerosis syndrome no assertion provided curation

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