ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1795G>A (p.Gly599Arg) (rs761959210)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438344 SCV000529744 uncertain significance not provided 2017-01-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TSC1 gene. The G599R variant was reported as a rare benign variant in both autism patients and in normal controls (Kelleher et al., 2012). The G599R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).The G599R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. Additionally, the vast majority of TSC1 pathogenic variants result in protein truncation, while missense variants have been reported only rarely (Northrup et al., 2011; Au et al., 2007). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000476022 SCV000552377 benign Tuberous sclerosis 1 2017-09-03 criteria provided, single submitter clinical testing

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