ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.2672dup (p.Asn891fs)

dbSNP: rs118203724
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000550474 SCV000641590 pathogenic Tuberous sclerosis 1 2021-08-16 criteria provided, single submitter clinical testing Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individuals affected with tuberous sclerosis complex (PMID: 9328481, 9803264, 9863590, 10363127). This variant is also known as 2887insA and 2887_2888insA in the literature. ClinVar contains an entry for this variant (Variation ID: 48989). This sequence change creates a premature translational stop signal (p.Asn891Lysfs*13) 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).
Ambry Genetics RCV001016278 SCV001177216 pathogenic Hereditary cancer-predisposing syndrome 2019-04-03 criteria provided, single submitter clinical testing The c.2672dupA pathogenic mutation, located in coding exon 19 of the TSC1 gene, results from a duplication of A at nucleotide position 2672, causing a translational frameshift with a predicted alternate stop codon (p.N891Kfs*13). This alteration has been identified in multiple individuals diagnosed with tuberous sclerosis and has been reported as 2887insA and 2887-2888insA in the literature (Jones AC et al. Hum. Mol. Genet., 1997 Nov;6:2155-61; Young JM et al. Ann. Hum. Genet., 1998 May;62:203-13; Ali JB et al. J. Med. Genet., 1998 Dec;35:969-72; Dabora SL et al. Ann. Hum. Genet., 1998 Nov;62:491-504). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Genome-Nilou Lab RCV000550474 SCV002040697 pathogenic Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000042240 SCV004848075 pathogenic Tuberous sclerosis syndrome 2019-02-01 criteria provided, single submitter clinical testing The p.Asn891fs variant in TSC1 has been reported in 5 individuals with tuberous sclerosis (Jones 1997, Ali 1998, Young 1998) and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 891 and leads to a premature termination codon 13 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the TSC1 gene is an established disease mechanism in individuals with tuberous sclerosis. In summary, this variant meets criteria to be classified as pathogenic for tuberous sclerosis in an autosomal dominant manner based upon predicted impact to the protein.
Tuberous sclerosis database (TSC1) RCV000042240 SCV000066026 not provided Tuberous sclerosis syndrome no assertion provided curation
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University RCV000550474 SCV001370509 pathogenic Tuberous sclerosis 1 2020-06-09 no assertion criteria provided clinical testing

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