ClinVar Miner

Submissions for variant NM_000137.4(FAH):c.880A>C (p.Thr294Pro)

gnomAD frequency: 0.00003  dbSNP: rs370634385
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004596 SCV001163760 likely pathogenic Tyrosinemia type I criteria provided, single submitter clinical testing
Invitae RCV001004596 SCV003521739 uncertain significance Tyrosinemia type I 2023-02-26 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 813491). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 294 of the FAH protein (p.Thr294Pro). This variant is present in population databases (rs370634385, gnomAD 0.007%). This missense change has been observed in individual(s) with tyrosinemia, type 1 (PMID: 8723690, 9633815). 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 not expected to disrupt FAH protein function. Experimental studies have shown that this missense change affects FAH function (PMID: 31300554). 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.

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