Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000755828 | SCV000883416 | uncertain significance | not provided | 2017-08-23 | criteria provided, single submitter | clinical testing | The p.His733Tyr variant (rs147531758) has been reported in the medical literature in a single individual with Charcot-Marie-Tooth (CMT) type 2 who also had a potentially pathogenic variant in the LMNA gene (Høyer 2014). It has also been identified by our laboratory in four individuals without a reported diagnosis of CMT, is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.19% in the non-Finnish European population (identified in 244 out of 126,604 chromosomes; 1 homozygote), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 157538). The histidine at codon 733 is highly conserved considering 12 species up to zebrafish (Alamut software v2.9.0); however, it is a tyrosine in armadillos, suggesting that this substitution may be evolutionary tolerated. Computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerate, PolyPhen2: probably damaging, MutationTaster: disease causing). Based on the available information, the clinical significance of the p.His733Tyr variant cannot be determined with certainty. |
Dept. |
RCV000144885 | SCV000118596 | uncertain significance | Charcot-Marie-Tooth disease | 2013-11-01 | no assertion criteria provided | research |