Submissions for variant NM_000368.5(TSC1):c.1773G>A (p.Pro591=)

gnomAD frequency: 0.00040  dbSNP: rs146578402

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228779	SCV000284684	benign	Tuberous sclerosis 1	2025-01-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000241773	SCV000303853	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000308169	SCV000478223	likely benign	Isolated focal cortical dysplasia type II	2017-04-28	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.
Illumina Laboratory Services, Illumina	RCV000228779	SCV000478224	likely benign	Tuberous sclerosis 1	2017-04-28	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.
GeneDx	RCV000241773	SCV000514999	benign	not specified	2015-09-28	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	RCV000571783	SCV000675386	likely benign	Hereditary cancer-predisposing syndrome	2016-07-06	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.
Genome-Nilou Lab	RCV000228779	SCV002040418	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000571783	SCV002530931	benign	Hereditary cancer-predisposing syndrome	2021-08-24	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000241773	SCV004221384	benign	not specified	2023-06-22	criteria provided, single submitter	clinical testing	The frequency of this variant in the general population (http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. Computational tools yielded predictions that this variant is unlikely to have an effect on normal RNA splicing. This nucleotide position exhibits low evolutionary conservation.
All of Us Research Program, National Institutes of Health	RCV003998771	SCV004819799	likely benign	Tuberous sclerosis syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000241773	SCV005622651	benign	not specified	2023-12-18	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000228779	SCV005881403	benign	Tuberous sclerosis 1	2025-02-01	criteria provided, single submitter	clinical testing