Variant: NM_000330.4(RS1):c.326+1G>A

CA226683

98936 (ClinVar)

Gene: RS1

Condition: X-linked retinoschisis

Inheritance Mode: X-linked inheritance (recessive (HP:0001419))

UUID: 46b1952f-ea42-4570-8d59-a19182066737

Approved on: 2025-05-19

Published on: 2025-05-20

HGVS expressions

NM_000330.4:c.326+1G>A
NM_000330.4(RS1):c.326+1G>A
NC_000023.11:g.18647190C>T
CM000685.2:g.18647190C>T
NC_000023.10:g.18665310C>T
CM000685.1:g.18665310C>T
NC_000023.9:g.18575231C>T
NG_008475.1:g.226586C>T
NG_008659.3:g.35259G>A
ENST00000379984.4:c.326+1G>A
ENST00000379984.3:c.326+1G>A
ENST00000379989.6:c.2797+1100C>T
ENST00000379996.7:c.2797+1100C>T
ENST00000476595.1:n.817+1G>A
NM_000330.3:c.326+1G>A
NM_001037343.1:c.2797+1100C>T
NM_003159.2:c.2797+1100C>T
NM_001037343.2:c.2797+1100C>T
NM_003159.3:c.2797+1100C>T

Pathogenic

• Met criteria codes: PS4_Supporting PVS1 PP1 PM2_Supporting

Expert Panel

X-linked Inherited Retinal Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

The NM_000330.4(RS1):c.326+1G>A variant is a canonical splice site variant in intron 4, located 1 nucleotide after exon 4. This variant occurs at a canonical splice site in intron 4 and is predicted to disrupt splicing and induce skipping of exon 5, which is expected to disrupt a critical functional domain in RS1 (PVS1). This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting). The variant has been reported to segregate with retinal dystrophy through 1 meiosis in a family with two affected brothers (PP1; PMID: 15937075). This variant has been reported in at least 2 apparently unrelated probands diagnosed with X-linked retinoschisis (PMID: 9618178, 15937075, 29099798, 30025115, 34822951, PS4_supporting). In summary, this variant is classified as pathogenic for X-linked retinoschisis based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0: PVS1, PM2_supporting, PS4_supporting, and PP1. (date of approval 01/24/2025).

Met criteria codes

• PS4_Supporting: This variant has been reported in at least 2 apparently unrelated probands diagnosed with XLRS (PMID: 9618178, 15937075, 29099798, 30025115, 34822951).
• PVS1: This variant occurs at a canonical splice site in intron 4 and is predicted to disrupt splicing and induce skipping of exon 5, which is expected to disrupt a critical functional domain in RS1 (PVS1).
• PP1: The variant has been reported to segregate with retinal dystrophy through 1 meiosis in a family two affected brothers. (PP1; PMID: 15937075).
• PM2_Supporting: This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting).