ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1766A>C (p.Gln589Pro) (rs397516422)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036458 SCV000060113 uncertain significance not specified 2013-02-05 criteria provided, single submitter clinical testing The Gln589Pro variant in SLC26A4 has not been reported in the literature nor pre viously identified by our laboratory. In addition, this variant has not been ide ntified in large and broad ethnically-matched populations by NHLBI Exome Sequenc ing Project ( Computational analyses (biochemi cal amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, addi tional information is needed to fully assess the clinical significance of the Gl n589Pro variant.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355805 SCV001550794 uncertain significance not provided no assertion criteria provided clinical testing The SLC26A4 p.Gln589Pro variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs397516422) and in ClinVar (classified as a VUS by Laboratory for Molecular Medicine). The variant was also identified in control databases in 4 of 282558 chromosomes at a frequency of 0.000014 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following population: European (non-Finnish) in 4 of 128944 chromosomes (freq: 0.000031), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. The p.Gln589 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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