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

dbSNP: rs45437193

Total submissions: 5

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