ClinVar Miner

Submissions for variant NM_012238.5(SIRT1):c.1417C>T (p.His473Tyr)

gnomAD frequency: 0.00001  dbSNP: rs751498023
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
Ambry Genetics RCV004249338 SCV003874183 uncertain significance not specified 2023-01-26 criteria provided, single submitter clinical testing The c.1417C>T (p.H473Y) alteration is located in exon 8 (coding exon 8) of the SIRT1 gene. This alteration results from a C to T substitution at nucleotide position 1417, causing the histidine (H) at amino acid position 473 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003565630 SCV004319249 uncertain significance not provided 2024-07-30 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 473 of the SIRT1 protein (p.His473Tyr). This variant is present in population databases (rs751498023, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SIRT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2459967). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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.

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.