ClinVar Miner

Submissions for variant NM_000137.3(FAH):c.696C>T (p.Asn232=) (rs533540262)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666812 SCV000791169 uncertain significance Tyrosinemia type I 2017-05-01 criteria provided, single submitter clinical testing
Invitae RCV000666812 SCV000955948 likely pathogenic Tyrosinemia type I 2018-10-19 criteria provided, single submitter clinical testing This sequence change affects codon 232 of the FAH mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FAH protein. This variant is present in population databases (rs533540262, ExAC 0.006%). This variant has been observed on the opposite chromosome (in trans) from pathogenic variants in individuals affected with tyrosinemia, type 1 (PMID: 8557261, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 551686). Experimental studies have shown that this silent change leads to the out-of-frame skipping of exon 8 from FAH mRNA (PMID: 8557261). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.