ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4255C>T (p.Gln1419Ter)

dbSNP: rs45437193
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000760367 SCV000890229 pathogenic not provided 2019-11-18 criteria provided, single submitter clinical testing Nonsense variant predicted to result in nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 10205261, 10090883, 12111193, 15121797, 17304050, 28065512)
Labcorp Genetics (formerly Invitae), Labcorp RCV001852897 SCV002131410 pathogenic Tuberous sclerosis 2 2023-09-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1419*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 10205261). ClinVar contains an entry for this variant (Variation ID: 49821). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002326762 SCV002627027 pathogenic Hereditary cancer-predisposing syndrome 2017-01-18 criteria provided, single submitter clinical testing The p.Q1419* variant (also known as c.4255C>T), located in coding exon 33 of the TSC2 gene, results from a C to T substitution at nucleotide position 4255. This changes the amino acid from a glutamine to a stop codon within coding exon 33. This mutation had been detected in multiple individuals meeting diagnostic criteria for tuberous sclerosis complex (TSC) (Jones AC et al. Am. J. Hum. Genet., 1999 May;64:1305-15; Cai Y et al. Urology, 2017 Jan; Roberts PS et al. J. Med. Genet., 2004 May;41:e69). 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.
Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service RCV000043087 SCV004698194 pathogenic Tuberous sclerosis syndrome 2024-01-11 criteria provided, single submitter clinical testing PVS1,PS4_Moderate
Tuberous sclerosis database (TSC2) RCV000043087 SCV000066886 not provided Tuberous sclerosis syndrome no assertion provided curation

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