Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000330.4:c.49G>T

CA412378947

Gene: RS1 (HGNC:6247)

Condition: X-linked retinoschisis (MONDO:0010725)

Inheritance Mode: X-linked inheritance

UUID: 28a36502-2f86-443f-b634-7029445d06be

Approved on: 2026-09-26

Published on: 2026-09-26

HGVS expressions

NM_000330.4:c.49G>T

NC_000023.11:g.18672020C>A

CM000685.2:g.18672020C>A

NC_000023.10:g.18690140C>A

CM000685.1:g.18690140C>A

NC_000023.9:g.18600061C>A

NG_008659.3:g.10429G>T

ENST00000379984.4:c.49G>T

ENST00000379984.3:c.49G>T

NM_000330.3:c.49G>T

Pathogenic

PM2_Supporting PVS1 PP4

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

NM_000330.4(RS1):c.49G>T (p.Glu17Ter) is a nonsense variant that introduces a premature stop codon in exon 1 of 6 and is predicted to trigger nonsense-mediated decay (PVS1). This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting). At least one proband harboring this variant exhibits a phenotype that includes the appearance of schisis and reduced visual acuity before age 13 years, which together are specific for X-linked retinoschisis (PMID: 30652005, PP4). 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: PM2_Supporting, PVS1, and PP4.

PM2_Supporting

This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting).

PVS1

This is a nonsense variant that introduces a premature stop codon between amino acids 1 and 223 that is predicted to either trigger nonsense-mediated decay or to disrupt a critical C-terminal region required for the proper function of RS1 (PVS1, PMID: 19849666).

PP4

At least one proband harboring this variant exhibits the following phenotypes, including the appearance of schisis and reduced visual acuity before age 13 years, which together are specific for X-linked retinoschisis (PMID: 30652005, PP4).

Curation History

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