Submissions for variant NM_000548.5(TSC2):c.5413G>A (p.Glu1805Lys)

dbSNP: rs376017665

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000644386	SCV000766079	benign	Tuberous sclerosis 2	2024-01-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001024065	SCV001186019	benign	Hereditary cancer-predisposing syndrome	2021-12-02	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV001119439	SCV001277838	likely benign	Tuberous sclerosis syndrome	2018-01-13	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.
Genome-Nilou Lab	RCV000644386	SCV002040300	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000644386	SCV002097690	uncertain significance	Tuberous sclerosis 2	2020-06-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004533370	SCV004116256	uncertain significance	TSC2-related disorder	2023-06-20	criteria provided, single submitter	clinical testing	The TSC2 c.5413G>A variant is predicted to result in the amino acid substitution p.Glu1805Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.059% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2138600-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Myriad Genetics, Inc.	RCV000644386	SCV005406231	likely benign	Tuberous sclerosis 2	2024-08-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.