ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.431T>A (p.Leu144Gln)

gnomAD frequency: 0.00001  dbSNP: rs1408195908
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001295177 SCV001484090 uncertain significance Usher syndrome type 3B 2020-07-08 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with HARS-related conditions. 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. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with glutamine at codon 144 of the HARS protein (p.Leu144Gln). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and glutamine.
Ambry Genetics RCV002462907 SCV002755844 uncertain significance Inborn genetic diseases 2021-05-14 criteria provided, single submitter clinical testing The p.L144Q variant (also known as c.431T>A), located in coding exon 5 of the HARS gene, results from a T to A substitution at nucleotide position 431. The leucine at codon 144 is replaced by glutamine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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