Submissions for variant NM_052859.4(RFT1):c.710G>A (p.Trp237Ter)

dbSNP: rs1408405816

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627314	SCV000748306	uncertain significance	not provided	2018-03-29	criteria provided, single submitter	clinical testing	The W237X variant in the RFT1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although not observed as homozygous, the W237X variant is observed in 1/15266 (0.0066%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). We interpret W237X as a variant of uncertain significance.
Invitae	RCV001855334	SCV002224304	uncertain significance	RFT1-congenital disorder of glycosylation	2022-04-15	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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 523841). This variant has not been reported in the literature in individuals affected with RFT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Trp237*) in the RFT1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in RFT1 cause disease.