Submissions for variant NM_001830.4(CLCN4):c.43G>A (p.Asp15Asn)

dbSNP: rs879255591

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Sydney Children's Hospital, SCHN	RCV000239753	SCV000266305	uncertain significance	CLCN4-related disorder	2016-03-22	criteria provided, single submitter	clinical testing	De novo variant. Additional non-neurological features not seen in other patients with CLCN4 related disorder.
GeneDx	RCV000441553	SCV000524775	likely pathogenic	not provided	2016-03-04	criteria provided, single submitter	clinical testing	The D15N variant in the CLCN4 gene has been previously reported in one individual with congenital diaphragmatic hernia (Yu et al., 2015). This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D15N variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. The D15N variant is asemi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The D15N variant is a strong candidate for a pathogenic variant.