ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1262A>C (p.Gln421Pro)

gnomAD frequency: 0.00003  dbSNP: rs201660407
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672119 SCV000797186 likely pathogenic Pendred syndrome 2018-01-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001386692 SCV001587029 pathogenic not provided 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 421 of the SLC26A4 protein (p.Gln421Pro). This variant is present in population databases (no rsID available, gnomAD 0.005%). This missense change has been observed in individual(s) with SLC26A4-related conditions (PMID: 17718863, 23918157, 24224479, 28964290). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 556159). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000770862 SCV002026921 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 2021-09-05 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000672119 SCV002026922 likely pathogenic Pendred syndrome 2021-09-05 criteria provided, single submitter clinical testing
3billion RCV000770862 SCV002573167 pathogenic Autosomal recessive nonsyndromic hearing loss 4 2022-09-01 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94; 3Cnet: 0.97). Same nucleotide change resulting in same amino acid change (ClinVar ID: VCV000556159 ) and different missense changes at the same codon (p.Gln421Arg, p.Gln421Leu/ ClinVar ID: VCV000430229 , VCV000691513 ) have been previously reported as pathogenic/likely pathogenic with strong evidence. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 23918157). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV000770862 SCV004204222 pathogenic Autosomal recessive nonsyndromic hearing loss 4 2023-01-27 criteria provided, single submitter clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital RCV000770862 SCV000902371 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 2019-02-26 no assertion criteria provided case-control

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