ClinVar Miner

Submissions for variant NM_016284.5(CNOT1):c.1603C>T (p.Arg535Cys)

dbSNP: rs1567417422
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
New York Genome Center RCV000758715 SCV001441383 pathogenic Holoprosencephaly sequence 2020-02-06 criteria provided, single submitter clinical testing The c.1603C>T (p.Arg535Cys) variant identified in the CNOT1 gene substitutes a highly conserved Arginine for Cysteine at amino acid 535/2377 (coding exon 14/49).This variant is absent from gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms predict this variant to be Deleterious (Provean; score: -6.83) and Damaging (SIFT; score: 0.000) to the function of the canonical transcript. This variant is reported as both Pathogenic and as a Variant of Uncertain Significance in ClinVar (VarID:619606). The p.Arg535Cys variant identified in this individual has been reported in five unrelated individuals with holoprosencephaly confirmed by MRI [PMID:31006513; PMID:31006510], or clinical features consistent with holoprosencephaly [PMID:31006513]. This variant was identified de novo in an individual submitted for clinical WGS. The c.1603C>T (p.Arg535Cys) variant identified in the CNOT1 gene is reported as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000787479 SCV002512576 pathogenic Holoprosencephaly 12 with or without pancreatic agenesis 2021-05-13 criteria provided, single submitter clinical testing ACMG classification criteria: PS4 moderate, PM1, PM2, PM6 very strong
Muenke lab, National Institutes of Health RCV000758715 SCV000887489 uncertain significance Holoprosencephaly sequence flagged submission clinical testing
OMIM RCV000787479 SCV000926444 pathogenic Holoprosencephaly 12 with or without pancreatic agenesis 2020-09-29 no assertion criteria provided literature only

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.