Submissions for variant NM_000368.5(TSC1):c.3428C>T (p.Pro1143Leu)

gnomAD frequency: 0.00003  dbSNP: rs201867031

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000274136	SCV000478171	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.
Illumina Laboratory Services, Illumina	RCV001081625	SCV000478172	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081625	SCV000641648	benign	Tuberous sclerosis 1	2025-01-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000572666	SCV000675369	likely benign	Hereditary cancer-predisposing syndrome	2022-01-07	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.
GeneDx	RCV000034611	SCV001774295	likely benign	not provided	2021-02-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30764584, 27023146, 22703879, 31875159)
Genome-Nilou Lab	RCV001081625	SCV002039988	likely benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001081625	SCV004360794	likely benign	Tuberous sclerosis 1	2022-03-14	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001081625	SCV005404877	likely benign	Tuberous sclerosis 1	2024-08-15	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.
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034611	SCV000043505	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.