Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000473593 | SCV000552248 | pathogenic | Tuberous sclerosis 1 | 2023-02-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln781*) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with tuberous sclerosis complex (PMID: 29500070, 32313033). ClinVar contains an entry for this variant (Variation ID: 48941). For these reasons, this variant has been classified as Pathogenic. |
Center for Genomics, |
RCV002054843 | SCV002496012 | pathogenic | Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II | 2021-03-30 | criteria provided, single submitter | clinical testing | TSC1 NM_000368.4 exon 18 p.Gln781* (c.2341C>T): This variant has been reported in several individuals with tuberous sclerosis in the Leiden Open-source Variation Database (LOVD) (https://databases.lovd.nl/shared/variants/TSC1). This variant is not present in large control databases but is present in ClinVar (Variation ID:48941). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is predicted to cause a stopgain at this codon, resulting in protein truncation or loss of allelic expression through nonsense-mediated mRNA decay. Loss of function variants are a known mechanism of disease for this gene (Rosset 2017 PMID:28222202). In summary, this variant is classified as pathogenic based on the data above. |
Ambry Genetics | RCV002426584 | SCV002731859 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-01-23 | criteria provided, single submitter | clinical testing | The p.Q781* pathogenic mutation (also known as c.2341C>T), located in coding exon 16 of the TSC1 gene, results from a C to T substitution at nucleotide position 2341. This changes the amino acid from a glutamine to a stop codon within coding exon 16. 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. |
Tuberous sclerosis database |
RCV000042192 | SCV000065978 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |