Submissions for variant NM_000218.3(KCNQ1):c.821TCT[1] (p.Phe275del)

dbSNP: rs397508126

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV000239632	SCV000805128	pathogenic	Long QT syndrome 1	2017-12-15	criteria provided, single submitter	clinical testing
Invitae	RCV001346356	SCV001540550	likely pathogenic	Long QT syndrome	2022-03-17	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this variant affects KCNQ1 function (PMID: 17655673). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 53112). This variant is also known as ΔF275. This variant has been observed in individuals with clinical features of KCNQ1-related conditions and/or long QT syndrome (PMID: 17655673, 27485560, 31737537; Invitae). This variant is not present in population databases (gnomAD no frequency). This variant, c.824_826del, results in the deletion of 1 amino acid(s) of the KCNQ1 protein (p.Phe275del), but otherwise preserves the integrity of the reading frame.
GeneDx	RCV001588868	SCV001826582	pathogenic	not provided	2019-09-17	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Reported in ClinVar as pathogenic (ClinVar Variant ID# 53112; Landrum et al., 2016); In-frame deletion of one amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Published functional studies demonstrate a loss-of-function when expressed in isolation and suggest dominant negative effect when co-expressed with the wildtype protein (Aizawa et al., 2007); This variant is associated with the following publications: (PMID: 31737537, 17655673, 27485560)
Dept of Medical Biology, Uskudar University	RCV001346356	SCV004021981	pathogenic	Long QT syndrome	2024-01-08	criteria provided, single submitter	research	Criteria: PS4_Strong, PS3_Moderate, PM2, PM4
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV000239632	SCV000255626	pathogenic	Long QT syndrome 1	2012-01-01	no assertion criteria provided	research