Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000670317 | SCV000795155 | uncertain significance | Tyrosinemia type I | 2017-10-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000670317 | SCV001576057 | pathogenic | Tyrosinemia type I | 2022-09-01 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects FAH function (PMID: 7550234, 11278491, 31300554). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FAH protein function. ClinVar contains an entry for this variant (Variation ID: 554643). This missense change has been observed in individual(s) with tyrosinemia type 1 (PMID: 7550234). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 234 of the FAH protein (p.Trp234Gly). For these reasons, this variant has been classified as Pathogenic. |