ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.1123C>T (p.Arg375Cys)

gnomAD frequency: 0.00002  dbSNP: rs774682373
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534421 SCV000652286 uncertain significance Usher syndrome type 3B 2023-07-21 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HARS protein function. ClinVar contains an entry for this variant (Variation ID: 472986). This variant has not been reported in the literature in individuals affected with HARS-related conditions. This variant is present in population databases (rs774682373, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 375 of the HARS protein (p.Arg375Cys).
GeneDx RCV001824342 SCV002074084 uncertain significance not provided 2022-02-01 criteria provided, single submitter clinical testing 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
Ambry Genetics RCV004024221 SCV003892700 uncertain significance not specified 2023-01-20 criteria provided, single submitter clinical testing The c.1123C>T (p.R375C) alteration is located in exon 10 (coding exon 10) of the HARS gene. This alteration results from a C to T substitution at nucleotide position 1123, causing the arginine (R) at amino acid position 375 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect - Invitae Patient Insights Network RCV001535484 SCV001749418 not provided Usher syndrome type 3; Usher syndrome type 3B; Autosomal dominant Charcot-Marie-Tooth disease type 2W no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 05-04-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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