Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000007910 | SCV001221475 | pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2019-03-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 136 of the HSPB1 protein (p.Arg136Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with Charcot-Marie-Tooth disease type 2 (PMID: 15122254). ClinVar contains an entry for this variant (Variation ID: 7482). This variant has been reported to affect HSPB1 protein function (PMID: 18344398, 20178975, 22031878, 22521462, 28797631). This variant disrupts the p.Arg136 amino acid residue in HSPB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21611841, 22176143, 25547330). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000007910 | SCV000028115 | pathogenic | Charcot-Marie-Tooth disease axonal type 2F | 2004-06-01 | no assertion criteria provided | literature only |