Submissions for variant NM_001256789.3(CACNA1F):c.2777G>A (p.Arg926His)

gnomAD frequency: 0.00005  dbSNP: rs782092924

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001039447	SCV001202977	uncertain significance	not provided	2024-12-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 937 of the CACNA1F protein (p.Arg937His). This variant is present in population databases (rs782092924, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CACNA1F-related conditions. ClinVar contains an entry for this variant (Variation ID: 837992). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1F protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV001039447	SCV004166310	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	CACNA1F: BS2
PreventionGenetics, part of Exact Sciences	RCV004754678	SCV005353600	likely benign	CACNA1F-related disorder	2024-09-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).