Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002543435 | SCV003522265 | uncertain significance | Axenfeld-Rieger syndrome type 3 | 2022-04-01 | criteria provided, single submitter | clinical testing | 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. 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. This missense change has been observed in individuals with congenital anomalies of the kidney and urinary tract (PMID: 32475988). 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 sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 364 of the FOXC1 protein (p.Pro364Ser). |
Yale Center for Mendelian Genomics, |
RCV001849735 | SCV002106748 | likely pathogenic | Congenital anomaly of kidney and urinary tract | 2020-06-01 | no assertion criteria provided | literature only |