Retinal disorders
Gene: HK1Submitted on behalf of NHS GMS "Amber or keep as green - dominant missense variant p.(Glu847Lys) reported many times in the literature." and "This gene is currently amber. It seems clear that the p.E847K variant is associated with retinal disease so I think that it should be green, even if retinal disease is restricted to this variant."Created: 8 Mar 2022, 10:06 a.m. | Last Modified: 8 Mar 2022, 10:06 a.m.
Panel Version: 2.243
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 10:06 a.m. | Last Modified: 8 Mar 2022, 10:27 a.m.
Panel Version: 2.243
This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. Based on the available information I do not think the variant found in multiple cases is due to a founder effect, because of this this gene should be considered to be promoted to Green status at the next review.Created: 12 Jan 2021, 10:49 a.m. | Last Modified: 12 Jan 2021, 10:49 a.m.
Panel Version: 2.120
Subsequent reported families are Asian, but with same recurrent missense. I am not convinced this is founder effect. Gene is associated with multiple phenotypes and this particular missense may have a specific effect that results in this particular phenotype. The variant is however present in 3 hets in gnomad (2 Asian, 1 European). This frequency may be compatible with AD retinitis pigmentosa.
However, also note PMID 30778173, where other mono-allelic variants have been linked to a neurodevelopmental disorder which includes visual impairment, and for this reason Green rating on this panel may still be appropriate.Created: 11 Oct 2020, 4:04 a.m. | Last Modified: 11 Oct 2020, 4:07 a.m.
Panel Version: 2.17
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Retinitis pigmentosa 79, MIM# 617460
Publications
I suspect this is worth keepingCreated: 30 Aug 2019, 2:12 p.m. | Last Modified: 30 Aug 2019, 2:12 p.m.
Panel Version: 1.159
Comment on list classification: More than 3 families reported, however seems to be a founder effect, therefore evidence for other variants in this gene is not yet established.Created: 15 Aug 2017, 8:03 a.m.
One missense variant reported so far. In PMID: 25190649 haplotype analysis in the 5 families, 3 of which were from the Acadian population in Louisiana, 1 French Canadian, and 1 Sicilian, demonstrated a shared 450-kb region on chromosome 10, suggesting a founder mutation.Created: 15 Aug 2017, 8 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Retinitis pigmentosa 79 617460
Publications
Phenotypes for gene: HK1 were changed from Retinitis pigmentosa 79, OMIM:617460; retinitis pigmentosa 79,MONDO:0044320 to Retinitis pigmentosa 79, OMIM:617460; Neurodevelopmental disorder with visual defects and brain anomalies, OMIM:618547
Phenotypes for gene: HK1 were changed from Retinitis pigmentosa 79, OMIM:617460, MONDO:0044320 to Retinitis pigmentosa 79, OMIM:617460; retinitis pigmentosa 79,MONDO:0044320
Tag for-review was removed from gene: HK1.
Source Expert Review Green was added to HK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag for-review tag was added to gene: HK1.
Publications for gene: HK1 were set to 25190649; 25316723
Phenotypes for gene: HK1 were changed from Retinitis pigmentosa 79 617460 to Retinitis pigmentosa 79, OMIM:617460, MONDO:0044320
Source NHS GMS was added to HK1.
This gene has been classified as Amber List (Moderate Evidence).
HK1 was added to Posterior segment abnormalitiespanel. Sources: Other
HK1 was created by ellenmcdonagh