Submissions for variant NM_001367624.2(ZNF469):c.5144G>A (p.Arg1715Lys)

gnomAD frequency: 0.00017  dbSNP: rs281865149

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001657701	SCV001873728	uncertain significance	not provided	2024-06-04	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has been reported in a patient with isolated keratoconus (PMID: 24895405); This variant is associated with the following publications: (PMID: 24895405)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001657701	SCV002261284	uncertain significance	not provided	2022-06-20	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1687 of the ZNF469 protein (p.Arg1687Lys). This variant is present in population databases (rs281865149, gnomAD 0.03%). This missense change has been observed in individual(s) with keratoconus (PMID: 24895405). ClinVar contains an entry for this variant (Variation ID: 126943). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277155	SCV002565359	uncertain significance	Ehlers-Danlos syndrome	2019-10-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336248	SCV002642749	uncertain significance	Cardiovascular phenotype	2021-07-29	criteria provided, single submitter	clinical testing	The p.R1687K variant (also known as c.5060G>A), located in coding exon 2 of the ZNF469 gene, results from a G to A substitution at nucleotide position 5060. The arginine at codon 1687 is replaced by lysine, an amino acid with highly similar properties. This variant was reported in a keratoconus cohort; however, clinical details were limited (Lechner J et al. Hum. Mol. Genet., 2014 Oct;23:5527-35). This amino acid position is poorly conserved in available 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.
Fulgent Genetics, Fulgent Genetics	RCV002477272	SCV002778035	uncertain significance	Brittle cornea syndrome 1	2021-10-05	criteria provided, single submitter	clinical testing
Willoughby Group, Queen's University Belfast	RCV000114799	SCV000148694	probable-pathogenic	Keratoconus 1		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.