Submissions for variant NM_133433.4(NIPBL):c.4321G>T (p.Val1441Leu)

dbSNP: rs727503769

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726375	SCV000344152	pathogenic	not provided	2016-08-18	criteria provided, single submitter	clinical testing
Invitae	RCV000157045	SCV000657495	pathogenic	Cornelia de Lange syndrome 1	2017-02-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. An experimental study has shown that this missense change alters RNA splicing, producing both a normal-length transcript that contains this missense change and a minor transcript that skips exon 20 and results in a frameshift (PMID: 20358602). This variant has been reported in many individuals affected with Cornelia de Lange syndrome (PMID: 24038889, 22857006, 25574841, 23254390, 24145515, 20358602). In several of these individuals, the variant arose de novo. ClinVar contains an entry for this variant (Variation ID: 180193). This variant is not present in population databases (rs727503769, ExAC no frequency). This sequence change replaces valine with leucine at codon 1441 of the NIPBL protein (p.Val1441Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine.
Revvity Omics, Revvity	RCV000157045	SCV002018337	pathogenic	Cornelia de Lange syndrome 1	2021-05-21	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000157045	SCV002054148	pathogenic	Cornelia de Lange syndrome 1	2021-07-15	criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000157045	SCV000195841	pathogenic	Cornelia de Lange syndrome 1	2014-12-02	no assertion criteria provided	research