Submissions for variant NM_000548.5(TSC2):c.4887C>T (p.Asp1629=)

gnomAD frequency: 0.00009  dbSNP: rs137854152

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000043239	SCV000395662	uncertain significance	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, 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.
GeneDx	RCV000431036	SCV000535093	likely benign	not specified	2018-01-25	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.
Invitae	RCV000464259	SCV000556506	benign	Tuberous sclerosis 2	2024-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000564650	SCV000675479	likely benign	Hereditary cancer-predisposing syndrome	2016-06-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000464259	SCV002040227	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000564650	SCV002533984	likely benign	Hereditary cancer-predisposing syndrome	2021-12-23	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003964898	SCV004778864	likely benign	TSC2-related condition	2023-08-14	criteria provided, single submitter	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).
Tuberous sclerosis database (TSC2)	RCV000043239	SCV000067040	not provided	Tuberous sclerosis syndrome		no assertion provided	curation