Submissions for variant NM_000368.5(TSC1):c.1648C>G (p.Gln550Glu)

gnomAD frequency: 0.00006  dbSNP: rs118203553

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000034603	SCV000514998	likely benign	not provided	2020-11-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29625052, 19747374, 21309039)
Ambry Genetics	RCV000569644	SCV000675394	likely benign	Hereditary cancer-predisposing syndrome	2018-03-14	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080934	SCV000763749	benign	Tuberous sclerosis 1	2023-12-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001080934	SCV001330309	likely benign	Tuberous sclerosis 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001167778	SCV001330310	likely benign	Isolated focal cortical dysplasia type II	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genome-Nilou Lab	RCV001080934	SCV002040427	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000569644	SCV002530919	likely benign	Hereditary cancer-predisposing syndrome	2021-08-10	criteria provided, single submitter	curation
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034603	SCV000043514	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
Tuberous sclerosis database (TSC1)	RCV000054849	SCV000065839	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000421357	SCV001740171	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034603	SCV001807380	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000034603	SCV001930539	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000034603	SCV001971441	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004745168	SCV005350535	likely benign	TSC1-related disorder	2024-03-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).