ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.2167C>G (p.His723Asp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001221275 SCV001393307 pathogenic not provided 2019-06-04 criteria provided, single submitter clinical testing This sequence change replaces histidine with aspartic acid at codon 723 of the SLC26A4 protein (p.His723Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with enlarged vestibular aqueduct (PMID: 19040761, 22289209, 25372295, 26035154). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. 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: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.His723 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11405873, 20583162, 22884721, 23755160, 24338212). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Precision Medicine Center,Zhengzhou University RCV001375680 SCV001572600 pathogenic Deafness, autosomal recessive 4, with enlarged vestibular aqueduct criteria provided, single submitter research PM2: gnomAD genomes East Asian allele frequency = 0.00005437<0.00007 PM3_VeryStrong: Pathogenic mutation confirmed in trans in two patients and phase unknown in four patients PM5: Another missense pathogenic variant (c.2168A>G, p.His723Arg) at the same codon PP3: REVEL score > 0.7 PP4: Patient's phenotype highly specific for gene

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