Submissions for variant NM_000751.3(CHRND):c.292A>G (p.Ile98Val)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002671797	SCV002990881	uncertain significance	Lethal multiple pterygium syndrome	2023-04-12	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHRND protein function. ClinVar contains an entry for this variant (Variation ID: 1952541). This variant has not been reported in the literature in individuals affected with CHRND-related conditions. This variant is present in population databases (rs781443298, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 98 of the CHRND protein (p.Ile98Val).