ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.946C>T (p.Arg316Trp) (rs535868591)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189844 SCV000243497 uncertain significance not provided 2016-09-02 criteria provided, single submitter clinical testing p.Arg316Trp (CGG>TGG): c.946 C>T in exon 10 of the TSC1 gene (NM_000368.3). The Arg316Trp missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Arg316Trp in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative as a positively charged Arginine residue is replaced by an uncharged Tryptophan residue and several in-silico algorithms predict it may be damaging to the structure/function of TSC1 protein. However, Arg316Trp alters a poorly conserved position in the protein and the vast majority of TSC1 mutations result in protein truncation, while missense mutations have been reported only rarely (Northrup et al., 2011; Au et al., 2007). Therefore, based on the currently available information, it is unclear whether Arg316Trp is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000458718 SCV000562470 benign Tuberous sclerosis 1 2016-05-18 criteria provided, single submitter clinical testing

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