ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.397G>A (p.Val133Ile) (rs118203381)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Gharavi Laboratory,Columbia University RCV000782214 SCV000920700 benign not provided 2018-09-16 criteria provided, single submitter research
Invitae RCV000456358 SCV000552363 uncertain significance Tuberous sclerosis 1 2018-07-29 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 133 of the TSC1 protein (p.Val133Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs118203381, ExAC 0.006%). This variant has been reported in an individual affected with tuberous sclerosis complex in the Leiden Open-source Variation Database (PMID: 21520333). However, in that individual a pathogenic allele was also identified in a different gene, which suggests that this c.397G>A variant was not the primary cause of disease. An experimental study has shown that this missense change does not significantly affect TSC1 protein activity or stability in vitro (PMID: 22161988). In summary, this variant is a rare missense change that does not affect protein function in vitro and has been reported to co-occur with a pathogenic variant. It is not expected to cause disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Tuberous sclerosis database (TSC1) RCV000054879 SCV000083094 not provided Tuberous sclerosis syndrome no assertion provided curation

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