ClinVar Miner

Submissions for variant NM_001605.3(AARS1):c.1001A>T (p.Tyr334Phe)

gnomAD frequency: 0.00001  dbSNP: rs527414180
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000559648 SCV000657649 likely benign Charcot-Marie-Tooth disease type 2 2024-05-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV002461354 SCV002755274 uncertain significance Inborn genetic diseases 2021-07-29 criteria provided, single submitter clinical testing The p.Y334F variant (also known as c.1001A>T), located in coding exon 7 of the AARS gene, results from an A to T substitution at nucleotide position 1001. The tyrosine at codon 334 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, this variant is unlikely to be causative of Charcot-Marie-Tooth disease, type 2N (AD); however, its contribution to the development of AARS-related early infantile epileptic encephalopathy (AR) is uncertain.
Neuberg Centre For Genomic Medicine, NCGM RCV003448322 SCV004176387 uncertain significance Developmental and epileptic encephalopathy, 29 2023-02-14 criteria provided, single submitter clinical testing The missense variant c.1001A>T (p.Tyr334Phe) in the AARS1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.007%) in the gnomAD Exomes and novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Tyrosine at position 334 is changed to a Phenylalanine changing protein sequence and it might alter its composition and physico- chemical properties. The amino acid change p.Tyr334Phe in AARS1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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