Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002272994 | SCV002557517 | uncertain significance | RFT1-congenital disorder of glycosylation | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. The following criteria are met: 0102 - Loss of function is a mechanism of disease in this gene and is associated with congenital disorder of glycosylation type In (MIM# 612015). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from an arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2) (1 heterozygote, 0 homozygotes). (SP) 0309 - Two alternative amino acid changes at the same position has been observed in gnomAD (v2) (p.(Arg37His): 13 heterozygotes, 0 homozygotes. p.(Arg37Ser): 1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 0704 - Another missense variant (p.(Arg37Leu)) comparable to the one identified in this case has limited previous evidence for pathogenicity and has been reported in one CDG patient (PMID: 26892341). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Invitae | RCV002272994 | SCV003009322 | uncertain significance | RFT1-congenital disorder of glycosylation | 2022-05-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 37 of the RFT1 protein (p.Arg37Cys). This variant is present in population databases (rs764833139, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RFT1-related conditions. 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 disruptive. 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 | RCV003096145 | SCV003562770 | uncertain significance | Inborn genetic diseases | 2021-07-08 | criteria provided, single submitter | clinical testing | The c.109C>T (p.R37C) alteration is located in exon 2 (coding exon 2) of the RFT1 gene. This alteration results from a C to T substitution at nucleotide position 109, causing the arginine (R) at amino acid position 37 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |