ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.2840C>A (p.Ala947Asp)

gnomAD frequency: 0.00007  dbSNP: rs368175948
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001214630 SCV001386319 uncertain significance Progressive familial heart block type IB 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 947 of the TRPM4 protein (p.Ala947Asp). This variant is present in population databases (rs368175948, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. ClinVar contains an entry for this variant (Variation ID: 944267). 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. 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 RCV002436823 SCV002748483 uncertain significance Cardiovascular phenotype 2024-03-24 criteria provided, single submitter clinical testing The p.A947D variant (also known as c.2840C>A), located in coding exon 19 of the TRPM4 gene, results from a C to A substitution at nucleotide position 2840. The alanine at codon 947 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002491663 SCV002779917 uncertain significance Progressive familial heart block type IB; Erythrokeratodermia variabilis et progressiva 6 2021-07-08 criteria provided, single submitter clinical testing

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