ClinVar Miner

Submissions for variant NM_052859.4(RFT1):c.454A>G (p.Lys152Glu)

gnomAD frequency: 0.00002  dbSNP: rs763862849
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001818462 SCV002064543 pathogenic not provided 2019-06-19 criteria provided, single submitter clinical testing DNA sequence analysis of the RFT1 gene demonstrated a sequence change, c.454A>G, in exon 4 that results in an amino acid change, p.Lys152Glu. This sequence change has been previously described in two patients in the homozygous state with neurological and clinical features of RFT1-related disorder (PMIDs: 19856127, 19701946). Expression of wild-type RFT1 in the patients? fibroblasts showed complementation of the abnormal lipid-linked oligosaccharide profile and reduced DNase 1 secretion, supporting RFT1 defect (PMID: 19701946). This sequence change has been described in the gnomAD database with a low population frequency of 0.0052% (dbSNP rs763862849). The p.Lys152Glu change affects a highly conserved amino acid residue located in a domain of the RFT1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Lys152Glu substitution. These collective evidences indicate that this sequence change is pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000190246 SCV002281115 likely pathogenic RFT1-congenital disorder of glycosylation 2024-11-06 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 152 of the RFT1 protein (p.Lys152Glu). This variant is present in population databases (rs763862849, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of RFT1-related conditions (PMID: 19701946, 19856127, 26892341, 27172925). ClinVar contains an entry for this variant (Variation ID: 207986). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mendelics RCV000190246 SCV002518978 pathogenic RFT1-congenital disorder of glycosylation 2022-05-04 criteria provided, single submitter clinical testing
OMIM RCV000190246 SCV000243770 pathogenic RFT1-congenital disorder of glycosylation 2009-12-01 no assertion criteria provided literature only

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