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Short QT syndrome v3.22 SLC4A3 Ida Ertmanska Publications for gene: SLC4A3 were set to 29167417; 29697308; 36806574; 18382206; 19862833; 30420954
Short QT syndrome v3.21 SLC4A3 Ida Ertmanska edited their review of gene: SLC4A3: Changed publications to: 36806574, 41039816
Short QT syndrome v3.21 SLC4A3 Ida Ertmanska changed review comment from: PMID: 36806574 Christiansen et al., 2023
Identified 4 patients with SQTS, heterozygous for novel nonsynonymous SLC4A3 variants: p.Arg600Cys, p.Arg621Trp, p.Glu852Asp, and p.Arg952His, and 1 patient with the known p.Arg370His variant.
Functional: Knockdown of slc4a3 in zebrafish resulted in shortened heart rate-corrected QT intervals. This was rescued by the WT human SLC4A3 protein expression, but not by the mutant proteins.

The relationship between SLC4A3 and Short QT syndrome was classified as Moderate in ClinGen (Short QT Syndrome GCEP, 2020).; to: PMID: 41039816 Crea et al., 2025
A novel heterozygous SLC4A3 mutation (c.1157G>T; p.Gly386Val) was identified in the proband and her mother, both with short QT intervals. The family history included multiple cases of sudden unexplained death and epilepsy

PMID: 36806574 Christiansen et al., 2023
Identified 4 patients with SQTS, heterozygous for novel nonsynonymous SLC4A3 variants: p.Arg600Cys, p.Arg621Trp, p.Glu852Asp, and p.Arg952His, and 1 patient with the known p.Arg370His variant.
Functional: Knockdown of slc4a3 in zebrafish resulted in shortened heart rate-corrected QT intervals. This was rescued by the WT human SLC4A3 protein expression, but not by the mutant proteins.

The relationship between SLC4A3 and Short QT syndrome was classified as Moderate in ClinGen (Short QT Syndrome GCEP, 2020).
Short QT syndrome v3.21 SLC4A3 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 13th May 2026.
Short QT syndrome v3.21 SLC4A3 Ida Ertmanska Phenotypes for gene: SLC4A3 were changed from short QT; ventricular fibrillation; cardiac arrest to Short QT syndrome 7, OMIM:620231; short QT syndrome 7, MONDO:0859368
Short QT syndrome v3.20 SLC4A3 Ida Ertmanska Publications for gene: SLC4A3 were set to 29167417; 29697308
Short QT syndrome v3.19 SLC4A3 Ida Ertmanska Mode of inheritance for gene: SLC4A3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v3.18 SLC4A3 Ida Ertmanska Classified gene: SLC4A3 as Amber List (moderate evidence)
Short QT syndrome v3.18 SLC4A3 Ida Ertmanska Added comment: Comment on list classification: There are now more than 3 unrelated patients with heterozygous SLC4A3 variants and short QT syndrome. Christiansen et al. (PMID: 36806574, 2023) pose that variants in SLC4A3 represent the most common cause of SQTS. Hence, this gene should be promoted to Green at the next update.
Short QT syndrome v3.18 SLC4A3 Ida Ertmanska Gene: slc4a3 has been classified as Amber List (Moderate Evidence).
Short QT syndrome v3.17 SLC4A3 Ida Ertmanska Tag Q2_26_promote_green tag was added to gene: SLC4A3.
Short QT syndrome v3.17 SLC4A3 Ida Ertmanska reviewed gene: SLC4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36806574; Phenotypes: Short QT syndrome 7, OMIM:620231, short QT syndrome 7, MONDO:0859368; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Short QT syndrome v1.25 SLC4A3 Ivone Leong Classified gene: SLC4A3 as Amber List (moderate evidence)
Short QT syndrome v1.25 SLC4A3 Ivone Leong Added comment: Comment on list classification: Demoted from Green to Amber based on the previously submitted review.
Short QT syndrome v1.25 SLC4A3 Ivone Leong Gene: slc4a3 has been classified as Amber List (Moderate Evidence).
Short QT syndrome v1.23 SLC4A3 Ivone Leong edited their review of gene: SLC4A3: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.; Changed rating: AMBER
Short QT syndrome v1.20 SLC4A3 James Eden reviewed gene: SLC4A3: Rating: AMBER; Mode of pathogenicity: None; Publications: 18382206, 19862833, 30420954; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v1.20 SLC4A3 Ivone Leong Source West Midlands, Oxford and Wessex GLH was added to SLC4A3.
Short QT syndrome v1.13 SLC4A3 Ivone Leong Added comment: Comment on mode of inheritance: Changed from Unknown back to Monoallelic after discussion with Anna de Burca (Genomics England).
Short QT syndrome v1.13 SLC4A3 Ivone Leong Mode of inheritance for gene: SLC4A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Short QT syndrome v1.10 SLC4A3 Rebecca Whittington commented on gene: SLC4A3: No associated phenotype on OMIM
Short QT syndrome v1.9 SLC4A3 Rebecca Whittington commented on gene: SLC4A3: 1 variant associated with SQT on HGMD
Short QT syndrome v1.8 SLC4A3 Rebecca Whittington reviewed gene: SLC4A3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Short QT syndrome v1.7 SLC4A3 Ellen McDonagh Source South West GLH was added to SLC4A3.
Mode of inheritance for gene SLC4A3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown
Short QT syndrome v1.2 SLC4A3 Oxford Medical Genetics Laboratory reviewed gene: SLC4A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Short QT syndrome v0.17 SLC4A3 Sarah Leigh Marked gene: SLC4A3 as ready
Short QT syndrome v0.17 SLC4A3 Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. One variant was identified in two unrelated families. The variant segregates with short QT in both families and an Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which was rescued by wildtype SLC4A3, but not by the variant (PMID: 29167417).
Short QT syndrome v0.17 SLC4A3 Sarah Leigh Gene: slc4a3 has been classified as Green List (High Evidence).
Short QT syndrome v0.3 SLC4A3 Sarah Leigh Publications for gene: SLC4A3 were set to PMID: 29167417; 29697308
Short QT syndrome v0.2 SLC4A3 Sarah Leigh Source Expert Review Green was added to SLC4A3.
Mode of inheritance for gene SLC4A3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Green List (high evidence)
Short QT syndrome v0.1 SLC4A3 Jules Hancox gene: SLC4A3 was added
gene: SLC4A3 was added to Short QT syndrome. Sources: Literature
Mode of inheritance for gene: SLC4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC4A3 were set to PMID: 29167417; 29697308
Phenotypes for gene: SLC4A3 were set to short QT; ventricular fibrillation; cardiac arrest
Review for gene: SLC4A3 was set to GREEN
Added comment: The Nature Communications paper reporting this association presents strong evidence for causal link to SQTS. This variant of the SQTS was found from exome sequencing. Mutation leads to altered pHi and decrease in intracellular chloride, which in turn abbreviates repolarization. The final mediator(s) of these actions remain to be elucidated.
Sources: Literature