Submissions for variant NM_000368.5(TSC1):c.73G>A (p.Val25Met)

gnomAD frequency: 0.00005  dbSNP: rs1230244328

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000642002	SCV000763655	likely benign	Tuberous sclerosis 1	2024-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001026391	SCV001188761	likely benign	Hereditary cancer-predisposing syndrome	2023-06-13	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	RCV001551730	SCV001772299	likely benign	not provided	2021-05-06	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30788456, 29636988, 31309300, 21520333)
Genome-Nilou Lab	RCV000642002	SCV002040516	likely benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004003957	SCV004840577	uncertain significance	Tuberous sclerosis syndrome	2023-11-30	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 25 of the TSC1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc.	RCV000642002	SCV005083357	likely benign	Tuberous sclerosis 1	2024-05-16	criteria provided, single submitter	clinical testing	This variant is considered likely benign. Homozygosity has been confirmed in one or more individuals. As homozygosity for pathogenic variants in this gene is generally assumed to result in embryonic lethality, this variant is unlikely to be pathogenic.