ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.451C>G (p.Gln151Glu) (rs371491165)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000416066 SCV000493534 uncertain significance not provided 2016-11-30 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000087309 SCV000120187 pathogenic Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy 2009-06-19 no assertion criteria provided literature only PMID:19542611 shows that this variant was identified in one patient with CADISIL. The affected amino acid is near cysteine residues in EGF repeats which may be important for protein conformation.
Fulgent Genetics,Fulgent Genetics RCV000764190 SCV000895192 uncertain significance Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; Lehman syndrome; Infantile myofibromatosis 2 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000416066 SCV000513945 uncertain significance not provided 2016-07-01 criteria provided, single submitter clinical testing The Q151E variant in the NOTCH3 gene has been reported previously in the heterozygous state in an individual with CADASIL, however familial segregation information was not included. (Ampuero et al., 2009). The Q151E variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q151E variant is a semi-conservative amino acid substitution, which occurs at a position that is well-conserved across species, however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on review of the data in the context of the 2015 ACMG standards and guidelines for the interpretation of sequence variants (Richards et al., 2015), we now interpret Q151E as a variant of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.