Submissions for variant NM_017636.4(TRPM4):c.24+6C>G

gnomAD frequency: 0.00013  dbSNP: rs767900879

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001700114	SCV000532490	likely benign	not provided	2020-12-31	criteria provided, single submitter	clinical testing
Invitae	RCV000645460	SCV000767205	uncertain significance	Progressive familial heart block type IB	2023-12-25	criteria provided, single submitter	clinical testing	This sequence change falls in intron 1 of the TRPM4 gene. It does not directly change the encoded amino acid sequence of the TRPM4 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs767900879, gnomAD 0.02%). 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: 389832). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Clinical Genetics, Academic Medical Center	RCV001700114	SCV001918235	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001700114	SCV001932193	likely benign	not provided		no assertion criteria provided	clinical testing