ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3125G>T (p.Ser1042Ile) (rs148931779)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189859 SCV000243512 uncertain significance not provided 2012-12-12 criteria provided, single submitter clinical testing p.Ser1042Ile (AGC>ATC): c.3125 G>T in exon 23 of the TSC1 gene (NM_000368.3). The Ser1042Ile 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 Ser1042Ile 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 polar Serine residue is replaced by a non-polar Isoleucine residue. It alters a highly conserved position in the protein. However, 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). Several in silico algorithms predict Ser1042Ile may be damaging to protein structure/function, while another model suggests it may be benign. Therefore, based on the currently available information, it is unclear whether Ser1042Ile is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000189859 SCV000552321 likely benign not provided 2019-01-26 criteria provided, single submitter clinical testing

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