Submissions for variant NM_005051.3(QARS1):c.1451del (p.Tyr484fs)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478623	SCV000570605	likely pathogenic	not provided	2016-06-10	criteria provided, single submitter	clinical testing	A novel c.1451delA variant that is likely pathogenic has been identified in the QARS gene. The c.1451delA variant causes a frameshift starting with codon Tyrosine 484, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 20 of the new reading frame, denoted p.Tyr484LeufsX20. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although this variant has not been previously reported to our knowledge, other loss-of-function variants have been reported in the Human Gene Mutation Database in association with QARS-related disorders (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002525873	SCV002239708	pathogenic	Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome	2024-09-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr484Leufs*20) in the QARS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in QARS are known to be pathogenic (PMID: 24656866, 25471517). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with QARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 421411). For these reasons, this variant has been classified as Pathogenic.

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