ClinVar Miner

Submissions for variant NM_003923.3(FOXH1):c.572C>T (p.Pro191Leu)

gnomAD frequency: 0.00001  dbSNP: rs1270394786
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001068470 SCV001233583 uncertain significance Holoprosencephaly sequence 2019-03-04 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 191 of the FOXH1 protein (p.Pro191Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FOXH1-related conditions. 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 leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV001759844 SCV001986675 uncertain significance not provided 2021-01-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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