Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002535932 | SCV000962596 | likely pathogenic | not provided | 2021-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with glutamine at codon 235 of the FH protein (p.His235Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with cutaneous leiomyomas and/or uterine fibroids (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 663861). 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 expected to disrupt FH protein function. 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. |