Submissions for variant NM_013275.6(ANKRD11):c.3562C>T (p.Arg1188Ter)

dbSNP: rs761848111

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000266509	SCV000330399	pathogenic	not provided	2017-11-08	criteria provided, single submitter	clinical testing	The R1188X variant in the ANKRD11 gene has not been reported previously as a pathogenic variant nor as a benignvariant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1188X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R1188X as a pathogenic variant.
Servicio de Genética Del Instituto Nacional de Salud Del Niño, Ministerio de Salud	RCV000578369	SCV005414461	pathogenic	KBG syndrome	2024-11-18	criteria provided, single submitter	clinical testing	The variant NM_001256182.2:p.Arg1188* introduces a premature stop codon at position 1188, which is likely to result in a truncated protein or nonsense-mediated decay (NMD). This is a loss-of-function variant that is predicted to disrupt normal protein function. Based on ACMG/AMP guidelines, this variant meets the criteria for PS4, PVS1, PM2, and PP5, supporting its classification as pathogenic. The evidence includes the loss of a critical functional domain due to the premature stop codon and the predicted deleterious effect of the variant.
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000578369	SCV000680115	pathogenic	KBG syndrome	2017-07-13	no assertion criteria provided	clinical testing