ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.410G>A (p.Arg137Gln) (rs191391414)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000033152 SCV000537217 pathogenic Charcot-Marie-Tooth disease, axonal, type 2w 2017-02-09 criteria provided, single submitter research
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514458 SCV000609999 uncertain significance not provided 2017-08-30 criteria provided, single submitter clinical testing
Invitae RCV000650143 SCV000771980 uncertain significance Usher syndrome, type 3B 2019-10-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 137 of the HARS protein (p.Arg137Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs191391414, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in several individuals affected with HARS-related conditions (PMID: 27353947, 29790872, 22930593). ClinVar contains an entry for this variant (Variation ID: 40062). This variant has been reported to affect HARS protein function (PMID: 22930593). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
OMIM RCV000033152 SCV000056934 pathogenic Charcot-Marie-Tooth disease, axonal, type 2w 2013-01-01 no assertion criteria provided literature only

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