Submissions for variant NM_001367624.2(ZNF469):c.7195C>T (p.Pro2399Ser)

gnomAD frequency: 0.00008  dbSNP: rs759032227

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000352275	SCV000399392	uncertain significance	Brittle cornea syndrome 1	2016-06-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001092211	SCV001248615	uncertain significance	not provided	2019-10-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001092211	SCV001815575	uncertain significance	not provided	2020-12-29	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001092211	SCV002127710	uncertain significance	not provided	2022-07-04	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2371 of the ZNF469 protein (p.Pro2371Ser). This variant is present in population databases (rs759032227, gnomAD 0.03%). 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: 320969). 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 serine 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.
MGZ Medical Genetics Center	RCV000352275	SCV002581327	uncertain significance	Brittle cornea syndrome 1	2022-02-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365386	SCV002662648	benign	Cardiovascular phenotype	2024-05-17	criteria provided, single submitter	clinical testing	This alteration is classified as 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.