Submissions for variant NM_024334.3(TMEM43):c.1105C>T (p.Leu369Phe)

gnomAD frequency: 0.00046  dbSNP: rs144152046

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039377	SCV000063061	benign	not specified	2019-09-24	criteria provided, single submitter	clinical testing	The p.Leu369Phe variant in TMEM43 is classified as benign because it has been identified in 0.1% (27/24964) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). Additionally, 5 species (cape elephant shrew, chicken, soft shell turtle, spiny soft shell turtle, and nile tilapia) carry a phenylalanine (Phe) at this position at this position despite high nearby amino acid conservation, suggesting that this change may be tolerated. Computational prediction tools support that this variant does not impact the protein. ACMG/AMP Criteria applied: BA1, BP4.
GeneDx	RCV001703890	SCV000236421	likely benign	not provided	2021-02-01	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21636032, 23812740)
Invitae	RCV000548269	SCV000642088	likely benign	Arrhythmogenic right ventricular dysplasia 5	2024-01-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001178613	SCV001343099	likely benign	Cardiomyopathy	2021-01-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426572	SCV002744024	likely benign	Cardiovascular phenotype	2018-11-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genetics, Academic Medical Center	RCV001703890	SCV001919591	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001703890	SCV001928228	likely benign	not provided		no assertion criteria provided	clinical testing