Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001587314 | SCV001826221 | likely pathogenic | not provided | 2024-03-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29205794, 30737337, 32369273, 32767731, 28000701, 35750896, 35982127, 36515421) |
Labcorp Genetics |
RCV001587314 | SCV005834408 | pathogenic | not provided | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 294 of the LARS2 protein (p.Glu294Lys). This variant is present in population databases (rs749627411, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of Perrault syndrome or deafness (PMID: 29205794, 30737337, 32767731, 35982127). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 992952). 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 LARS2 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV001283750 | SCV001469096 | pathogenic | Perrault syndrome 4 | 2021-01-15 | no assertion criteria provided | literature only | |
Gene |
RCV002542964 | SCV003525953 | not provided | Perrault syndrome | no assertion provided | literature only |