ClinVar Miner

Submissions for variant NM_001367624.2(ZNF469):c.2898GTCGGG[1] (p.967SG[1])

dbSNP: rs281865147
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002433604 SCV002751874 uncertain significance Cardiovascular phenotype 2021-10-13 criteria provided, single submitter clinical testing The c.2904_2909delGTCGGG variant (also known as p.S969_G970del) is located in coding exon 1 of the ZNF469 gene. This variant results from an in-frame GTCGGG deletion at nucleotide positions 2904 to 2909. This results in the in-frame deletion two amino acids at codon 969. The nucleotide and amino acid positions are poorly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002509221 SCV002819927 uncertain significance not specified 2022-12-31 criteria provided, single submitter clinical testing Variant summary: ZNF469 c.2904_2909delGTCGGG (p.Ser969_Gly970del) results in an in-frame deletion that is predicted to remove 2 amino acids from the encoded protein. The variant allele was found at a frequency of 1.4e-05 in 143044 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2904_2909delGTCGGG has been reported in the literature in the heterozygous state in at least one individual with keratoconus (Lechner_2014). This report does not provide unequivocal conclusions about association of the variant with Brittle Cornea Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV003556163 SCV004297039 uncertain significance not provided 2023-12-10 criteria provided, single submitter clinical testing This variant, c.2904_2909del, results in the deletion of 2 amino acid(s) of the ZNF469 protein (p.Ser969_Gly970del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with clinical features of ZNF469-related conditions (PMID: 24895405). 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.
Willoughby Group, Queen's University Belfast RCV000114796 SCV000148691 pathogenic Keratoconus 1 no assertion criteria provided not provided Converted during submission to Pathogenic.

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