Submissions for variant NM_172362.3(KCNH1):c.2020C>T (p.Arg674Trp)

dbSNP: rs754794236

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002130460	SCV002442548	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002272566	SCV002557927	uncertain significance	KCNH1 associated disorder	2022-09-02	criteria provided, single submitter	clinical testing	A heterozygous missense variant was identified, NM_172362.2(KCNH1):c.2020C>T in exon 10 of 11 of the KCNH1 gene. This substitution is predicted to create a major amino acid change from an arginine to a tryptophan at position 674 of the protein; NP_758872.1(KCNH1):p.(Arg674Trp). The arginine at this position has very high conservation (100 vertebrates, UCSC), and is located within the CAP_ED functional domain (NCBI). In silico software predicts this variant to be damaging (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.00040% (1 heterozygote, 0 homozygotes). An alternative residue change at the same location has been reported in the gnomAD database at a frequency of 0.0040%. This variant has not previously been reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VUS.