Submissions for variant NM_001367624.2(ZNF469):c.941C>T (p.Pro314Leu)

gnomAD frequency: 0.00013  dbSNP: rs777666112

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001955814	SCV002224131	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 314 of the ZNF469 protein (p.Pro314Leu). This variant is present in population databases (rs777666112, gnomAD 0.01%). 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: 1444075). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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	RCV002370586	SCV002687143	uncertain significance	Cardiovascular phenotype	2023-03-23	criteria provided, single submitter	clinical testing	The c.941C>T (p.P314L) alteration is located in exon 1 (coding exon 1) of the ZNF469 gene. This alteration results from a C to T substitution at nucleotide position 941, causing the proline (P) at amino acid position 314 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002497830	SCV002776937	uncertain significance	Brittle cornea syndrome 1	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001955814	SCV003923977	uncertain significance	not provided	2022-11-10	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
CeGaT Center for Human Genetics Tuebingen	RCV001955814	SCV004138055	uncertain significance	not provided	2023-04-01	criteria provided, single submitter	clinical testing	ZNF469: PM2
Mayo Clinic Laboratories, Mayo Clinic	RCV001955814	SCV005411377	uncertain significance	not provided	2024-09-19	criteria provided, single submitter	clinical testing	BP4