ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.1007C>G (p.Pro336Arg)

dbSNP: rs2128134025
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001378844 SCV001576522 likely pathogenic Charcot-Marie-Tooth disease type 2 2020-05-20 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with congenital hypomyelinating polyneuropathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 336 of the GARS protein (p.Pro336Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001751749 SCV002006876 uncertain significance not provided 2020-07-08 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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