ClinVar Miner

Submissions for variant NM_017547.4(FOXRED1):c.1454T>A (p.Ile485Asn)

gnomAD frequency: 0.00004  dbSNP: rs770063137
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000518955 SCV000621231 uncertain significance not provided 2017-10-05 criteria provided, single submitter clinical testing The I485N variant in the FOXRED1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I485N variant is observed in 10/34332 (0.029%) alleles from individuals of Latino background, in the ExAC dataset (Lek et al., 2016). The I485N variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I485N as a variant of uncertain significance.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678792 SCV000804973 uncertain significance Developmental delay 2017-08-09 criteria provided, single submitter clinical testing
Baylor Genetics RCV001334925 SCV001527936 uncertain significance Leigh syndrome 2018-11-26 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV000518955 SCV002193321 uncertain significance not provided 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 485 of the FOXRED1 protein (p.Ile485Asn). This variant is present in population databases (rs770063137, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FOXRED1-related conditions. ClinVar contains an entry for this variant (Variation ID: 452423). 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. 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 RCV002527642 SCV003695679 uncertain significance Inborn genetic diseases 2021-10-29 criteria provided, single submitter clinical testing The c.1454T>A (p.I485N) alteration is located in exon 11 (coding exon 11) of the FOXRED1 gene. This alteration results from a T to A substitution at nucleotide position 1454, causing the isoleucine (I) at amino acid position 485 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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