Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000533118 | SCV000657704 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-06-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 265 of the GARS protein (p.Ser265Phe). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GARS function (PMID: 25168514). 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. ClinVar contains an entry for this variant (Variation ID: 476762). This variant is also known as p.Ser211Phe. This missense change has been observed in individuals with Charcot-Marie-Tooth disease and/or distal hereditary motor neuropathy type V (PMID: 23279345, 27862672; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). |
| Eurofins Ntd Llc |
RCV000734019 | SCV000862130 | likely pathogenic | not provided | 2018-07-18 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics Inc | RCV000734019 | SCV001879804 | pathogenic | not provided | 2020-10-02 | criteria provided, single submitter | clinical testing | This variant is also referred to as c.632C>T (p.Ser211Phe) in published literature. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant appears to segregate with disease in at least one family, however, the available information does not rule out segregation due to chance. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant leads to aberrant binding to HDAC6, resulting in reduced alpha-tubulin acetylation, which impairs axonal transportation (PMID: 29520015). Experimental results also indicate this variant severely impairs native aminoacylation activity (PMID: 25168514), however the loss of this function is not related to peripheral neuropathy (PMID: 30643024). Computational tools predict that this variant is damaging. |
| Inherited Neuropathy Consortium | RCV000789776 | SCV000929160 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
| Inherited Neuropathy Consortium Ii, |
RCV003447146 | SCV004174563 | uncertain significance | Neuronopathy, distal hereditary motor, type 5 | 2016-01-06 | no assertion criteria provided | literature only |