Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000644311 | SCV000766004 | likely benign | Tuberous sclerosis 2 | 2023-12-26 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001023719 | SCV001185634 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-01 | criteria provided, single submitter | clinical testing | The p.D1734N variant (also known as c.5200G>A), located in coding exon 40 of the TSC2 gene, results from a G to A substitution at nucleotide position 5200. The aspartic acid at codon 1734 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been identified in a Chinese colorectal cancer patient who was diagnosed at age 30 (Zhang JX et al. World J Gastroenterol, 2015 Apr;21:4136-49) as well as in a patient with autism spectrum disorder (D'Gama AM et al. Neuron, 2015 Dec;88:910-917). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV000644311 | SCV002040259 | likely benign | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Clinical Genomics Laboratory, |
RCV003456111 | SCV004177156 | uncertain significance | Tuberous sclerosis syndrome | 2023-08-06 | criteria provided, single submitter | clinical testing | The TSC2 c.5200G>A (p.Asp1734Asn) variant has been reported in one individual affected with colorectal cancer (Zhang JX et al., PMID: 25892863). This variant has been classified in the ClinVar database as likely benign by two submitters and uncertain significance by one submitter (ClinVar ID 536037). TSC2 c.5200G>A (p.Asp1734Asn) is only observed on 4/152196 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors indicate that the variant is damaging, evidence that correlates with impact to TSC2 protein function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain. |