Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756817 | SCV000884737 | uncertain significance | not provided | 2017-07-21 | criteria provided, single submitter | clinical testing | The variant p.Ala380Val (rs150894548) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.01 percent in the African population (identified on 3 out of 23,990 chromosomes). The alanine at position 380 is highly conserved considering twelve species (Alamut v2.9.0) and computational analyses of the effects of the p.Ala380Val variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Ala380Val variant with certainty. |
| Center for Advanced Laboratory Medicine, |
RCV000852481 | SCV000995176 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2018-01-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001045338 | SCV001209179 | uncertain significance | Progressive familial heart block type IB | 2024-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 380 of the TRPM4 protein (p.Ala380Val). This variant is present in population databases (rs150894548, gnomAD 0.01%). This missense change has been observed in individual(s) with a sudden unexpected death (PMID: 30391667). ClinVar contains an entry for this variant (Variation ID: 618448). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects TRPM4 function (PMID: 30391667). 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. |
| Ambry Genetics | RCV002325455 | SCV002607263 | uncertain significance | Cardiovascular phenotype | 2023-04-20 | criteria provided, single submitter | clinical testing | The p.A380V variant (also known as c.1139C>T), located in coding exon 9 of the TRPM4 gene, results from a C to T substitution at nucleotide position 1139. The alanine at codon 380 is replaced by valine, an amino acid with similar properties. This variant has been detected in a sudden death victim, and one group reported this variant to result in abnormal protein trafficking and to impact channel function in in vitro functional studies (Subbotina E et al. Forensic Sci. Int., 2018 Dec;293:37-46). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002485959 | SCV002787395 | uncertain significance | Progressive familial heart block type IB; Erythrokeratodermia variabilis et progressiva 6 | 2021-08-10 | criteria provided, single submitter | clinical testing |