ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.2521G>A (p.Gly841Ser) (rs369259434)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000426450 SCV000535462 uncertain significance not provided 2017-01-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NOTCH1 gene. The G841S variant has not beenpublished as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observedwith any significant frequency in approximately 6,200 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In addition,the G841S variant is a non-conservative amino acid substitution, which is likely to impact secondary proteinstructure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at aposition that is not conserved, and serine (S) is tolerated in multiple species. Finally, two of three in silico modelspredict this variant likely does not alter the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.This result cannot be interpreted for diagnosis or used for family member screening at this time.
Blueprint Genetics RCV000157394 SCV000207132 uncertain significance Arterial dissection 2014-10-06 no assertion criteria provided clinical testing

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