Retinal disorders

Gene: HK1

Submitted 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

Green List (high evidence)

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

• 25316723
• 25190649
• 31621442
• 32814480
• 30778173

I don't know

I suspect this is worth keeping

Created: 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

• 25190649
• 25316723