Mackenzie's Mission_Reproductive Carrier Screening

Gene: KCNE1

I don't know

Comment by Ivan Macciocca:
as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group:
Genetic evidence associating this gene with disease causality was also based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS, although studies in large families with variant
segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS.

Comment by Zornitza Stark:
Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited.

Additional: Technically challenging as only coding exon has reduced mappability and putative (but disputed) pseudogene KCNE1B that was introduced in GRCh38, but is not present in GRCh37/hg19 (PMID31527855, PMID30936463)

Association with Long-QT is questionable. Remains GREEN for Deafness, but on balance does not currently meet inclusion criteria for Mackenzie's Mission

Created: 16 Oct 2020, 6:02 a.m. | Last Modified: 16 Oct 2020, 6:08 a.m.

Panel Version: 0.31

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Long QT syndrome 5, MIM# 613695; Jervell and Lange-Nielsen syndrome 2, MIM# 612347; Acquired LQTS

Publications

• 31527855
• 30936463
• 31983240

Green List (high evidence)

Note different genome builds have differences in mappability

Created: 16 Oct 2020, 4:07 a.m. | Last Modified: 16 Oct 2020, 4:07 a.m.

Panel Version: 0.27

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal