ClinVar Miner

Submissions for variant NM_052859.4(RFT1):c.1331C>T (p.Thr444Met)

gnomAD frequency: 0.00039  dbSNP: rs147740901
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV000660602 SCV000782718 uncertain significance RFT1-congenital disorder of glycosylation 2017-09-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000660602 SCV000897134 uncertain significance RFT1-congenital disorder of glycosylation 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000660602 SCV000953415 uncertain significance RFT1-congenital disorder of glycosylation 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 444 of the RFT1 protein (p.Thr444Met). This variant is present in population databases (rs147740901, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of congenital disorder of glycosylation (PMID: 38374194). ClinVar contains an entry for this variant (Variation ID: 547993). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RFT1 protein function with a negative predictive value of 80%. 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.
Illumina Laboratory Services, Illumina RCV000660602 SCV001306059 uncertain significance RFT1-congenital disorder of glycosylation 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV001592843 SCV001822340 uncertain significance not provided 2020-09-04 criteria provided, single submitter clinical testing Reported in the heterozygous state in a patient with central serous chorioretinopathy who also harbored several variants in other genes (Schellevis et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30724488)
Ambry Genetics RCV002530579 SCV003715575 uncertain significance Inborn genetic diseases 2021-06-19 criteria provided, single submitter clinical testing The c.1331C>T (p.T444M) alteration is located in exon 12 (coding exon 12) of the RFT1 gene. This alteration results from a C to T substitution at nucleotide position 1331, causing the threonine (T) at amino acid position 444 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000660602 SCV003816121 uncertain significance RFT1-congenital disorder of glycosylation 2021-12-30 criteria provided, single submitter clinical testing

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