Retinal disorders

Gene: SAG

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 1:02 p.m. | Last Modified: 11 Mar 2026, 1:02 p.m.

Panel Version: 8.97

Green List (high evidence)

Comment on mode of inheritance: There is sufficient evidence for the association of both monoallelic and biallelic SAG variants with phenotypes relevant to retinal disorders panel. Hence, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.

Created: 15 Oct 2025, 12:59 p.m. | Last Modified: 15 Oct 2025, 12:59 p.m.

Panel Version: 8.46

Comment on phenotypes: Both monoallelic and biallelic variants in SAG gene are associated with relevant phenotypes in OMIM (MIMs #258100, #613758 & #620228). OMIM records were accessed on 15 October 2025.

Created: 15 Oct 2025, 12:57 p.m. | Last Modified: 15 Oct 2025, 12:58 p.m.

Panel Version: 8.45

PMID:28549094 (2017) reported the identification of a novel heterozygous variant in the SAG gene (c.440G>T/ p.Cys147Phe) in eight families in a cohort of 300 autosomal dominant retinitis pigmentosa (adRP) families. There were four additional families with adRP were reported in this study with the same heterozygous variant. All 12 families are of Hispanic descent from South Western United States. Haplotype analysis was consistent with a founder mutation event and a distant relationship between all of the families. The mutation dramatically alters a conserved amino acid, is extremely rare in global databases, and was not found in 4000+ exomes from Hispanic controls.

PMID:33047631 (2021) reported the identification of the same variant p.Cys147Phe variant in a 3-generation Australian family segregating with adRP. The mutation was found in the proband, his brother, and the brother's affected son, as well as in the proband's asymptomatic 10-year-old son who had not been examined. The variant was not found in the brother's asymptomatic son, who had a normal retinal examination at age 35 years.

PMID:40461169 (2025) reported the identification of a novel heterozygous SAG variant (c.442G>A/ p.Gly148Arg) in five unrelated families of Southern Chinese descent from Singapore with adRP. A shared haplotype of 3.2 Mb among four families suggested a founder effect.

The 'founder-effect' tag has been added as the two reported heterozygous variants are suggested to be founder variants.

Created: 15 Oct 2025, 12:52 p.m. | Last Modified: 15 Oct 2025, 1 p.m.

Panel Version: 8.46

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Oguchi disease-1, OMIM:258100; Retinitis pigmentosa 47, autosomal recessive, OMIM:613758; Retinitis pigmentosa 96, autosomal dominant, OMIM:620228

Publications

• 28549094
• 33047631
• 40461169

Green List (high evidence)

Already green with a biallelic MOI.

More recently, a single autosomal dominant variant Cys147Phe has been reported associated with retinitis pigmentosa

Created: 21 Dec 2024, 7:06 p.m. | Last Modified: 21 Dec 2024, 7:06 p.m.

Panel Version: 7.1

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 28549094
• 33047631

Mode of pathogenicity
Other

Green List (high evidence)

This gene is on the Manchester Genetic Retinal Degeneration Conditions panel (covers known genes for isolated progessive retinal degeneration, Leber congenital amaurosis, macular dystrophy, achromatopsia, congenital stationary night blindness as well as the two most common causes of syndromic blindess Usher and Bardet-Biedl syndromes and additional syndromes including Joubert, Senior-Loken, and Cohen syndrome.

Created: 2 Jun 2016, 8:05 a.m.