ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.3000C>G (p.Cys1000Trp)

dbSNP: rs552217429
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000688208 SCV000815810 likely benign Tuberous sclerosis 1 2024-07-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV003372807 SCV004097349 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-12 criteria provided, single submitter clinical testing The p.C1000W variant (also known as c.3000C>G), located in coding exon 21 of the TSC1 gene, results from a C to G substitution at nucleotide position 3000. The cysteine at codon 1000 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004004278 SCV004829143 uncertain significance Tuberous sclerosis syndrome 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tryptophan at codon 1000 of the TSC1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC1-related disorders in the literature. This variant has been identified in 1/247322 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV005251169 SCV005902419 uncertain significance not provided 2024-09-25 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV004723070 SCV005338565 uncertain significance TSC1-related disorder 2024-07-01 no assertion criteria provided clinical testing The TSC1 c.3000C>G variant is predicted to result in the amino acid substitution p.Cys1000Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00090% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/567988/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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