Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000524753 | SCV000652294 | uncertain significance | Usher syndrome type 3B | 2024-08-29 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 18 of the HARS protein (p.Val18Met). This variant is present in population databases (rs774632798, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with HARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 472993). 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 disruptive. 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. |
ARUP Laboratories, |
RCV001001086 | SCV001158221 | uncertain significance | not specified | 2019-03-04 | criteria provided, single submitter | clinical testing | The HARS c.52G>A; p.Val18Met variant (rs774632798), to our knowledge, is not described in the medical literature but contains an entry in ClinVar (Variation ID: 472993). It is observed in the general population at an overall frequency of 0.005% (14/278134 alleles) in the Genome Aggregation Database. The valine at codon 18 is moderately conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. |
Prevention |
RCV003409814 | SCV004115369 | uncertain significance | HARS1-related disorder | 2023-02-20 | criteria provided, single submitter | clinical testing | The HARS1 c.52G>A variant is predicted to result in the amino acid substitution p.Val18Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0086% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-140070838-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ambry Genetics | RCV001001086 | SCV005129125 | likely benign | not specified | 2024-03-28 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |