ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1973A>C (p.Lys658Thr) (rs397515223)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000122212 SCV000243664 uncertain significance not specified 2015-08-12 criteria provided, single submitter clinical testing p.Lys658Thr (AAG>ACG): c.1973 A>C in exon 19 of the TSC2 gene (NM_000548.3)The Lys658Thr missense substitution in TSC2 has not been published as a mutation or reported as a benign polymorphsim to our knowledge. The amino acid substitution is non-conservative, as a positively charged Lysine is replaced by an uncharged Threonine residue, and it alters a position that is highly conserved in the TSC2 protein and in related proteins. Some In vitro studies indicate that Lys658Thr does not significantly alter TSC2 protein function, suggesting it is likely a benign variant (Hoogeveen-Westerveld et al., 2011). Additionally, deletion of the Lys658 residue is reported as a rare benign variant in an external database, indicating that this amino acid is not required for normal protein function (TSC2 LOVD). These findings suggest that Lys658Thr is likely a rare benign variant; however, the possibility that it is a disease-causing mutation cannot be excluded. The variant is found in INFANT-EPI panel(s).
Invitae RCV000234257 SCV000285264 benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000055529 SCV000395597 uncertain significance Tuberous sclerosis syndrome 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564486 SCV000675536 likely benign Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Subpopulation frequency in support of benign classification;Other data supporting benign classification
Tuberous sclerosis database (TSC2) RCV000055529 SCV000083752 not provided Tuberous sclerosis syndrome no assertion provided curation
ITMI RCV000122212 SCV000086433 not provided not specified 2013-09-19 no assertion provided reference population

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