Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003517129 | SCV004292168 | uncertain significance | Lethal multiple pterygium syndrome | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 79 of the CHRND protein (p.Ile79Lys). This variant is present in population databases (rs121909509, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of autosomal recessive CHRND-related conditions (PMID: 18398509, 29399782). This variant is also known as I58K. ClinVar contains an entry for this variant (Variation ID: 18365). 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 expected to disrupt CHRND protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CHRND function (PMID: 18398509). 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. |
OMIM | RCV000020033 | SCV000040331 | pathogenic | Congenital myasthenic syndrome 3B | 2008-05-01 | no assertion criteria provided | literature only |