Submissions for variant NM_000368.4(TSC1):c.2209-3T>C (rs368309229)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000467930	SCV000478209	uncertain significance	Tuberous sclerosis 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina	RCV000357586	SCV000478210	likely benign	Focal cortical dysplasia type II	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000467930	SCV000552330	benign	Tuberous sclerosis 1	2019-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000610023	SCV000732285	likely benign	not specified	2018-02-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV001014788	SCV001175544	uncertain significance	Hereditary cancer-predisposing syndrome	2018-12-12	criteria provided, single submitter	clinical testing	The c.2209-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 16 in the TSC1 gene. This alteration is predicted to slightly decrease the efficiency of the native splice acceptor site by the BDGP in silico model and is not predicted to have a deleterious effect on splicing by the ESEfinder tool; however experimental evidence is not currently available. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.