ClinVar Miner

Submissions for variant NM_005051.3(QARS1):c.1170G>A (p.Met390Ile)

gnomAD frequency: 0.00001  dbSNP: rs1559967769
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV000694739 SCV001480400 uncertain significance Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome 2020-04-20 criteria provided, single submitter clinical testing The homozygous c.1170G>A (p.Met390Ile) variant identified in the QARS1 gene substitutes a well conserved Methionine for Isoleucine at amino acid 390/776 (coding exon 14/24). This variant is found with low frequency in gnomAD (2 heterozygotes, 0 homozygotes; allele frequency: 1.40e-5) suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms predict this variant to be Deleterious (Provean; score: -3.68) and Damaging (SIFT; score:0.000) to the function of the canonical transcript. This variant is reported as a Variant of Uncertain Significance in ClinVar (VarID:573149) and to our current knowledge has not been reported in affected individuals in the literature. The p.Met390 residue is within the catalytic domain of QARS1 (UniProtKB; P47897), where other missense variants have been reported [PMID:32042906; PMID:25471517]. Given the lack of compelling evidence for its pathogenicity, the homozygous c.1170G>A (p.Met390Ile) variant identified in the QARS1 gene is reported here as a Variant of Uncertain Significance.
GeneDx RCV001571716 SCV001796236 uncertain significance not provided 2024-02-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 25471517)
Labcorp Genetics (formerly Invitae), Labcorp RCV001571716 SCV002129084 uncertain significance not provided 2021-08-12 criteria provided, single submitter clinical testing

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