ClinVar Miner

Submissions for variant NM_153717.3(EVC):c.1018C>T (p.Arg340Ter)

gnomAD frequency: 0.00003  dbSNP: rs121908425
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255270 SCV000322261 pathogenic not provided 2016-02-05 criteria provided, single submitter clinical testing The R340X pathogenic variant in the EVC gene has been reported previously in Ellis-van Creveldsyndrome, in an affected individual who was compound heterozygous for the R340X variant andanother protein truncating variant (Ruiz-Perez et al., 2000). This variant is predicted to cause loss ofnormal protein function either through protein truncation or nonsense-mediated mRNA decay. TheR340X variant was not observed in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. We interpret R340X as a pathogenic variant.
Rare Disease Group, Clinical Genetics, Karolinska Institutet RCV000005668 SCV000788394 pathogenic Ellis-van Creveld syndrome 2018-05-01 criteria provided, single submitter research
Invitae RCV000807465 SCV000947518 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2023-09-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg340*) in the EVC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EVC are known to be pathogenic (PMID: 23220543). This variant is present in population databases (rs121908425, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with EVC-related conditions (PMID: 10700184, 17024374, 29068549). ClinVar contains an entry for this variant (Variation ID: 5340). For these reasons, this variant has been classified as Pathogenic.
3billion RCV000005668 SCV002058980 pathogenic Ellis-van Creveld syndrome 2022-01-03 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000005340, PMID:10700184).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000014, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity RCV000255270 SCV003823855 pathogenic not provided 2022-09-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000255270 SCV004562442 pathogenic not provided 2023-09-05 criteria provided, single submitter clinical testing The EVC c.1018C>T; p.Arg340Ter variant (rs121908425) is reported in the literature in multiple individuals affected with Ellis-van Creveld syndrome and Weyers acrofacial dyostosis (Ruiz-Perez 2000, Stranneheim 2021). This variant is also reported in ClinVar (Variation ID: 5340) and is found in the general population with an allele frequency of 0.001414% (4/282,890 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Several downstream truncating variants have been described in individuals with Ellis-van Creveld syndrome and are considered pathogenic (Nguyen 2016, Ruiz-Perez 2000). Based on the available information, this variant is considered to be pathogenic. References: Nguyen TQ et al. Truncation and microdeletion of EVC/EVC2 with missense mutation of EFCAB7 in Ellis-van Creveld syndrome. Congenit Anom (Kyoto). 2016 Sep;56(5):209-16. PMID: 26748586. Ruiz-Perez VL et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet. 2000;24(3):283-286. PMID: 10700184. Stranneheim H et al. Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients. Genome Med. 2021;13(1):40. Published 2021 Mar 17. PMID: 33726816.
OMIM RCV000005668 SCV000025850 pathogenic Ellis-van Creveld syndrome 2000-03-01 no assertion criteria provided literature only
Dan Cohn Lab, University Of California Los Angeles RCV000516113 SCV000612079 pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly 2017-06-01 no assertion criteria provided research
Counsyl RCV000005668 SCV000795981 pathogenic Ellis-van Creveld syndrome 2017-11-26 no assertion criteria provided clinical testing
Natera, Inc. RCV000005668 SCV001454799 pathogenic Ellis-van Creveld syndrome 2020-09-16 no assertion criteria provided clinical testing
University of Washington Center for Mendelian Genomics, University of Washington RCV000516113 SCV001479594 likely pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly no assertion criteria provided research

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.