Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002527442 | SCV003439238 | uncertain significance | Usher syndrome type 3B | 2022-03-14 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects HARS function (PMID: 29235198, 32543048). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 446300). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 26752306, 29235198). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 330 of the HARS protein (p.Tyr330Cys). |
Antonellis Laboratory at Michigan, |
RCV000515533 | SCV000611613 | uncertain significance | Autosomal dominant Charcot-Marie-Tooth disease type 2W | no assertion criteria provided | in vitro |