Submissions for variant NM_001792.5(CDH2):c.1471G>C (p.Val491Leu)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002765980	SCV003023406	uncertain significance	not provided	2025-01-12	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 491 of the CDH2 protein (p.Val491Leu). This variant is present in population databases (rs201148355, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CDH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1978900). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	RCV003274018	SCV003975582	uncertain significance	Inborn genetic diseases	2023-06-07	criteria provided, single submitter	clinical testing	The c.1471G>C (p.V491L) alteration is located in exon 10 (coding exon 10) of the CDH2 gene. This alteration results from a G to C substitution at nucleotide position 1471, causing the valine (V) at amino acid position 491 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
WangQJ Lab, Chinese People's Liberation Army General Hospital	RCV003483894	SCV004229039	likely pathogenic	Auditory neuropathy	2023-12-22	criteria provided, single submitter	research