ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.2774A>C (p.Lys925Thr)

gnomAD frequency: 0.00019  dbSNP: rs752778561
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001978 SCV001159786 uncertain significance Progressive familial heart block type IB 2018-07-18 criteria provided, single submitter clinical testing The TRPM4 c.2774A>C; p.Lys925Thr variant (rs752778561), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in non-Finnish European population with an overall allele frequency of 0.0036% (4/111358 alleles) in the Genome Aggregation Database. The lysine at codon 925 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Lys925Thr variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001001978 SCV001382503 uncertain significance Progressive familial heart block type IB 2024-08-01 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 925 of the TRPM4 protein (p.Lys925Thr). This variant is present in population databases (rs752778561, gnomAD 0.004%). 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: 811697). 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 RCV002434394 SCV002746571 uncertain significance Cardiovascular phenotype 2023-11-03 criteria provided, single submitter clinical testing The c.2774A>C (p.K925T) alteration is located in exon 18 (coding exon 18) of the TRPM4 gene. This alteration results from a A to C substitution at nucleotide position 2774, causing the lysine (K) at amino acid position 925 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002505530 SCV002814088 uncertain significance Progressive familial heart block type IB; Erythrokeratodermia variabilis et progressiva 6 2021-09-21 criteria provided, single submitter clinical testing

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