ClinVar Miner

Submissions for variant NM_153717.3(EVC):c.89C>T (p.Pro30Leu) (rs886044558)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000398177 SCV000345425 uncertain significance not provided 2016-08-26 criteria provided, single submitter clinical testing
Invitae RCV000536411 SCV000634730 uncertain significance Ellis-van Creveld syndrome; Curry-Hall syndrome 2017-06-29 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 30 of the EVC protein (p.Pro30Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a EVC-related disease. ClinVar contains an entry for this variant (Variation ID: 290794). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on EVC function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000398177 SCV000883812 uncertain significance not provided 2017-07-14 criteria provided, single submitter clinical testing The p.Pro30Leu has not been reported in the scientific literature and gene specific variant databases. However, the p.Pro30Leu is listed in ClinVar with current classification of uncertain significance (Variation ID 290794). This variant is listed in the Genome Aggregation Consortium Browser with an overall allele frequency of 0.12 percent (identified on 31 out of 25,982 chromosomes) but it was indicated as a low quality site. Additionally, proline 30 is moderately conserved considering 12 species (Alamut software v2.9.0) and computational prediction programs do not agree in their assessment of an impact of this variant on the protein (SIFT: tolerated, PolyPhen-2: benign, and MutationTaster: disease causing).
Illumina Clinical Services Laboratory,Illumina RCV001153149 SCV001314411 uncertain significance Ellis-van Creveld syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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