ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4544_4547del (p.Asn1515fs) (rs137854175)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000201030 SCV000255903 pathogenic Tuberous sclerosis 2 2014-12-19 criteria provided, single submitter clinical testing
Invitae RCV000201030 SCV000285408 pathogenic Tuberous sclerosis 2 2018-08-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1515Serfs*60) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. This variant has been reported in the literature in several individuals affected with tuberous sclerosis (PMID: 15595939, 11112665, 12111193, 9302281). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is also known in the literature as c.4562_4565delACAA and c.4559 del 4bps. ClinVar contains an entry for this variant (Variation ID: 49304). Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000360616 SCV000329788 pathogenic not provided 2016-06-21 criteria provided, single submitter clinical testing The c.4544_4547delACAA pathogenic variant in the TSC2 gene has been reported previously multiple times in association with tuberous sclerosis complex (Maheshwar et al., 1997, Ali et al., 2005, TSC2 LOVD). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The deletion causes a frameshift starting with codon Asparagine 1515, changes this amino acid to a Serine residue and creates a premature Stop codon at position 60 of the new reading frame, denoted p.Asn1515SerfsX60. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000360616 SCV000709284 pathogenic not provided 2017-06-21 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000042563 SCV000066356 not provided Tuberous sclerosis syndrome no assertion provided curation
Tuberous sclerosis database (TSC2) RCV000042563 SCV000066357 not provided Tuberous sclerosis syndrome no assertion provided curation

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