Submissions for variant NM_015443.4(KANSL1):c.1816C>T (p.Arg606Ter) (rs281865469)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523815	SCV000617313	pathogenic	not provided	2018-07-05	criteria provided, single submitter	clinical testing	The R606X variant in the KANSL1 gene has been reported previously as a de novo variant in an individual with intellectual disability, hypotonia, and friendly behavior (Zollino et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R606X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R606X as a pathogenic variant.
SIB Swiss Institute of Bioinformatics	RCV000024371	SCV000994930	pathogenic	Koolen-de Vries syndrome	2019-06-05	criteria provided, single submitter	curation	This variant is interpreted as a Pathogenic for Koolen-De Vries syndrome, autosomal dominant. The following ACMG Tag(s) were applied: PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6: Assumed de novo, but without confirmation of paternity and maternity. PVS1: Predicted nullvariant in a gene where LOF is a known mechanism of disease.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001255390	SCV001431790	pathogenic	Global developmental delay	2019-11-01	criteria provided, single submitter	clinical testing
OMIM	RCV000024371	SCV000045664	pathogenic	Koolen-de Vries syndrome	2012-04-29	no assertion criteria provided	literature only
GeneReviews	RCV000024371	SCV000055761	pathologic	Koolen-de Vries syndrome	2012-11-20	no assertion criteria provided	curation	Converted during submission to Pathogenic.