Submissions for variant NM_017780.4(CHD7):c.2894A>G (p.Asn965Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005089117	SCV005720548	uncertain significance	CHARGE syndrome	2024-12-24	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 965 of the CHD7 protein (p.Asn965Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHD7-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CHD7 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV005323724	SCV005983988	uncertain significance	Inborn genetic diseases	2025-01-20	criteria provided, single submitter	clinical testing	The c.2894A>G (p.N965S) alteration is located in exon 11 (coding exon 10) of the CHD7 gene. This alteration results from a A to G substitution at nucleotide position 2894, causing the asparagine (N) at amino acid position 965 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.