ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.989dup (p.Ser331fs) (rs118203478)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491374 SCV000579945 pathogenic Hereditary cancer-predisposing syndrome 2016-04-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Athena Diagnostics Inc RCV000201139 SCV000255870 pathogenic Tuberous sclerosis 1 2014-07-09 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000201139 SCV000782383 pathogenic Tuberous sclerosis 1 2016-11-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414909 SCV000492767 pathogenic Renal insufficiency; Renal cortical cysts; Cortical dysplasia 2015-10-21 criteria provided, single submitter clinical testing
GeneDx RCV000189866 SCV000243519 pathogenic not provided 2016-12-14 criteria provided, single submitter clinical testing The c.989dupT nonsense variant in the TSC1 gene has been reported multiple times previously inassociation with TSC (van Slegtenhorst, et al., 1999 using alternative nomenclature 1210insT; TSC1LOVD). The duplication causes a frameshift starting with codon Serine 331, changes this amino acidto a Glutamic acid residue and creates a premature Stop codon at position 10 of the new reading frame,denoted p.Ser331GlufsX10. This pathogenic variant is predicted to cause loss of normal proteinfunction either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV000201139 SCV000931870 pathogenic Tuberous sclerosis 1 2018-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser331Glufs*10) in the TSC1 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 an individuals affected with tuberous sclerosis complex (PMID: 23341583, 10227394, 28968464, 10570911). This variant is also known as c.990insT and c.1210insT in the literature. ClinVar contains an entry for this variant (Variation ID: 49135). Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC1) RCV000042390 SCV000066180 not provided Tuberous sclerosis syndrome no assertion provided curation

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