ClinVar Miner

Submissions for variant NM_001371333.1(DIABLO):c.179C>T (p.Ala60Val)

gnomAD frequency: 0.00016  dbSNP: rs199898020
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000222051 SCV000271643 uncertain significance not specified 2016-01-04 criteria provided, single submitter clinical testing The p.Ala60Val variant in DIABLO has not been previously reported in individuals with hearing loss and has been identified in 14/66736 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1 99898020). Although this variant has been seen in the general population, its f requency is not high enough to rule out a pathogenic role. The alanine (Ala) at position 60 is not well conserved across species, with 1 mammal and several bird s and reptiles having a valine (Val) at this position, suggesting that a change to a valine residue at this position may be tolerated. Additional computational prediction tools do not provide strong support for or against an impact the prot ein. In summary, while the clinical significance of the p.Ala60Val variant is u ncertain.
GeneDx RCV001799636 SCV002043974 likely benign not provided 2021-12-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015)
Ambry Genetics RCV000222051 SCV003865212 uncertain significance not specified 2023-02-23 criteria provided, single submitter clinical testing The c.179C>T (p.A60V) alteration is located in exon 3 (coding exon 2) of the DIABLO gene. This alteration results from a C to T substitution at nucleotide position 179, causing the alanine (A) at amino acid position 60 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001799636 SCV004275684 uncertain significance not provided 2024-12-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 60 of the DIABLO protein (p.Ala60Val). This variant is present in population databases (rs199898020, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with 36515421 (DIABLO-related conditions). ClinVar contains an entry for this variant (Variation ID: 228570). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.

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