Description
A heterozygous missense variant, NM_000220.4(KCNJ1):c.659T>G, has been identified in exon 2 of 2 of the KCNJ1 gene (NB: This gene is also known as Kir1.1). The variant is predicted to result in a major amino acid change from a leucine to an arginine at position 220 of the protein, NP_000211.1(KCNJ1):p.(Leu220Arg). The leucine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the IRK potassium channel domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.00041% (1 heterozygote, 0 homozygote). An alternate change within the same residue, p.(Leu220Phe) was also present in gnomAD at a frequency of 0.037% (89 heterozygotes, 0 homozygotes). This variant has not been previously reported in clinical cases. However, a different variant in the same codon resulting in a change to a phenylalanine, p.(Leu220Phe) have been observed as a compound heterozygote with a second missense variant in two families with Barrter syndrome (Vollmer, M., et al. (1998), Srivastava, S., et al. (2013)). Analysis of parental samples indicated this variant was maternally inherited. Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | maternal | yes | not provided | not provided | not provided | | 2 | not provided | 1 | not provided |
