ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.2077G>C (p.Asp693His) (rs397514800)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724243 SCV000226569 uncertain significance not provided 2014-12-15 criteria provided, single submitter clinical testing
GeneDx RCV000724243 SCV000243506 uncertain significance not provided 2013-09-24 criteria provided, single submitter clinical testing p.Asp693His (GAC>CAC): c.2077 G>C in exon 17 of the TSC1 gene (NM_000368.4). The Asp693His missense change has been reported in an external database in an individual who had another disease-causing mutation, and functional analysis of the variant predicts that it is likely a neutral change (Hoogeveen-Westerveld et al., 2011). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of a negatively charged Aspartic acid residue with a positively charged Histidine residue at a position that is not conserved across species. Additionally, 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). In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Asp693His is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV001083507 SCV000284694 benign Tuberous sclerosis 1 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564681 SCV000675370 likely benign Hereditary cancer-predisposing syndrome 2018-09-17 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s)
Tuberous sclerosis database (TSC1) RCV000054914 SCV000083129 not provided Tuberous sclerosis syndrome no assertion provided curation

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