ClinVar Miner

Submissions for variant NM_001367624.2(ZNF469):c.5548C>A (p.Pro1850Thr)

gnomAD frequency: 0.00092  dbSNP: rs199932922
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000375933 SCV000399364 uncertain significance Brittle cornea syndrome 1 2016-06-14 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000513538 SCV000608783 likely benign not provided 2023-11-01 criteria provided, single submitter clinical testing ZNF469: BP4
Baylor Genetics RCV000375933 SCV001526474 uncertain significance Brittle cornea syndrome 1 2018-03-11 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV000513538 SCV001795205 likely benign not provided 2020-11-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 29111844, 24895405)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002278460 SCV002565365 uncertain significance Ehlers-Danlos syndrome 2021-01-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348062 SCV002649749 likely benign Cardiovascular phenotype 2019-06-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000513538 SCV003257067 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1822 of the ZNF469 protein (p.Pro1822Thr). This variant is present in population databases (rs199932922, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with keratoconus (PMID: 24895405). ClinVar contains an entry for this variant (Variation ID: 320941). 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: "Deleterious"; 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.

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