ClinVar Miner

Submissions for variant NM_001367624.2(ZNF469):c.4907A>G (p.His1636Arg)

gnomAD frequency: 0.00020  dbSNP: rs557636016
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000307640 SCV000399354 uncertain significance Brittle cornea syndrome 1 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001859905 SCV002311382 uncertain significance not provided 2022-10-19 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1608 of the ZNF469 protein (p.His1608Arg). This variant is present in population databases (rs557636016, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. ClinVar contains an entry for this variant (Variation ID: 320932). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002338908 SCV002635057 uncertain significance Cardiovascular phenotype 2019-11-12 criteria provided, single submitter clinical testing The p.H1608R variant (also known as c.4823A>G), located in coding exon 2 of the ZNF469 gene, results from an A to G substitution at nucleotide position 4823. The histidine at codon 1608 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species, and arginine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003922357 SCV004738098 uncertain significance ZNF469-related disorder 2023-11-30 no assertion criteria provided clinical testing The ZNF469 c.4823A>G variant is predicted to result in the amino acid substitution p.His1608Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.056% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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