Submissions for variant NM_000368.5(TSC1):c.2968G>A (p.Glu990Lys)

gnomAD frequency: 0.00003  dbSNP: rs200398750

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226388	SCV000284712	benign	Tuberous sclerosis 1	2024-01-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000573300	SCV000675372	likely benign	Hereditary cancer-predisposing syndrome	2018-06-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000226388	SCV001332259	uncertain significance	Tuberous sclerosis 1	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, 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 Laboratory Services, Illumina	RCV001169544	SCV001332260	likely benign	Isolated focal cortical dysplasia type II	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.
GeneDx	RCV001536549	SCV001753324	likely benign	not provided	2019-12-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000226388	SCV002040027	likely benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000573300	SCV002528912	likely benign	Hereditary cancer-predisposing syndrome	2021-02-17	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV003998776	SCV004840450	likely benign	Tuberous sclerosis syndrome	2023-11-02	criteria provided, single submitter	clinical testing