SLMAP

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: ClinGen

SLMAP encodes the Sarcolemmal Membrane–Associated Protein, a protein initially purified from cardiac tissue and described to exist in three isoforms: SLMAP1 - 3 (PMID: 9405447). While the function of this gene is not well characterised, SLMAP has been implicated in biological processes such as muscle contraction (PMID: 30856349). Ishikawa et al. first suggested an association between SLMAP variants and autosomal dominant Brugada syndrome in 2012, following screening of a cohort of 190 Japanese patients (PMID: 23064965). Transfection of these variants in cell models resulted in decreased Nav1.5 surface expression and sodium current, prompting the authors to suggest a mechanism involving defective Nav1.5 trafficking. However, these variants are now known to be too common in the East Asian population to cause autosomal dominant Brugada syndrome. Since this initial report, there have been no further publications reporting SLMAP variants in the context of Brugada syndrome. There has only been one case report detailing a 20-year-old man who experienced a sudden death without clear cause and who carried a variant of unknown significance in SLMAP (p.Ser200Leu) (PMID: 34067575). Further, no rare SLMAP variants were identified by Di Resta et al. in their cohort of 91 patients with SCN5A-negative Brugada syndrome (PMID: 26220970). The cardiac overexpression of the SLMAP1-TM2 isoform in mice has been reported to cause ventricular dysfunction including a prolonged QT interval with dilation of the sarcoplasmic/endoplasmic reticulum (Nadar et al. PMID: 22180652). Additionally, the cardiac overexpression of SLMAP3 in mice was observed to cause systolic dysfunction with decreased fractional shortening, cardiac output and increased PR intervals (PMID: 30934005). The implication of these studies for the potential pathogenesis of SLMAP variants is unclear. SLMAP was originally classified as disputed for Brugada syndrome by the ClinGen Brugada Syndrome Gene Curation Expert Panel in 2017. This gene-disease relationship was re-evaluated on November 25, 2025, by the Hereditary Cardiovascular Disorders GCEP. Following re-evaluation, the gene-disease classification was refuted. This classification was approved by the ClinGen HCVD GCEP on November 25, 2025 (in accordance with SOP Version 11).

Inheritance Pattern: Unknown

Disease ID:MONDO:0015263

Submitter: Genomics England PanelApp

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: Orphanet

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: G2P