Submissions for variant NM_000548.5(TSC2):c.4046C>T (p.Ala1349Val)

gnomAD frequency: 0.00001  dbSNP: rs201979616

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000034656	SCV000243701	likely benign	not provided	2021-02-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22703879)
Ambry Genetics	RCV000215282	SCV000277729	likely benign	Hereditary cancer-predisposing syndrome	2021-07-12	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.
Invitae	RCV001081977	SCV000544338	benign	Tuberous sclerosis 2	2024-01-03	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV001081977	SCV000890931	uncertain significance	Tuberous sclerosis 2	2023-05-31	criteria provided, single submitter	clinical testing	The TSC2 c.4046C>T (p.Ala1349Val) missense change has a maximum subpopulation frequency of 0.011% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. This variant has been reported in an individual with tuberous sclerosis complex who also harbored a second missense variant in TSC2 (LOVD database). The phase of these variants is unknown. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Genome-Nilou Lab	RCV001081977	SCV002039815	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000215282	SCV002533492	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-12	criteria provided, single submitter	curation
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034656	SCV000043539	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.