ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.3325A>G (p.Met1109Val)

dbSNP: rs1845043842
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001045909 SCV001209784 uncertain significance Tuberous sclerosis 1 2019-03-13 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TSC1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 1109 of the TSC1 protein (p.Met1109Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine.
Ambry Genetics RCV002320262 SCV002607300 likely benign Hereditary cancer-predisposing syndrome 2021-08-25 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.

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