ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.3505C>T (p.His1169Tyr)

gnomAD frequency: 0.00002  dbSNP: rs747562782
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000385270 SCV000449975 uncertain significance Ellis-van Creveld syndrome 2018-01-13 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850852 SCV002161339 uncertain significance Ellis-van Creveld syndrome; Curry-Hall syndrome 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 1169 of the EVC2 protein (p.His1169Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs747562782, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with EVC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 348982). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004619269 SCV005113339 uncertain significance Inborn genetic diseases 2024-05-12 criteria provided, single submitter clinical testing The c.3505C>T (p.H1169Y) alteration is located in exon 20 (coding exon 20) of the EVC2 gene. This alteration results from a C to T substitution at nucleotide position 3505, causing the histidine (H) at amino acid position 1169 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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