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

dbSNP: rs281865147

Total submissions: 4

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.
Labcorp Genetics (formerly Invitae), Labcorp	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.