Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000594329 | SCV000706604 | uncertain significance | not provided | 2017-02-24 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV001449843 | SCV001653145 | likely benign | not specified | 2020-09-28 | criteria provided, single submitter | clinical testing | The p.Val735Ile variant in LARS2 is classified as likely benign due to a lack of conservation across species. Twelve mammals (rhesus, baboon, crab-eating macaque, alpaca, dolphin, killer whale, David's myotis, microbat, big brown bat, opossum, Tasmanian devil, wallaby) carry a isoleucine (Ile) at this position despite high nearby amino acid conservation. It has also been identified in 0.1% (30/24904) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BP4_Strong, BS1_Supporting. |
| Gene |
RCV000594329 | SCV001785553 | uncertain significance | not provided | 2022-02-09 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV000594329 | SCV002166109 | uncertain significance | not provided | 2022-06-15 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 735 of the LARS2 protein (p.Val735Ile). This variant is present in population databases (rs141011840, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with LARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 500586). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |