Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001806833 | SCV002051390 | uncertain significance | not specified | 2021-12-01 | criteria provided, single submitter | clinical testing | Variant summary: SLC26A4 c.1286C>A (p.Ala429Glu) results in a non-conservative amino acid change located in the SLC26A/SulP transporter domain (IPR011547) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250856 control chromosomes, predominantly at a frequency of 0.00033 within the East Asian subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1286C>A has been reported in the literature in Chinese individuals affected with hearing loss and Pendred Syndrome (e.g. Hunag_2011, Zhao_2014, Chen_2016, Chen_2018, Wen_2019, Luo_2021). Two of the studies reported the variant in compound heterozygosity with the pathogenic variant c.919-2A>G; one of these patients was affected with nonsyndromic enlargement of vestibular aqueduct (Zhao_2014), while the other patient was unaffected and had normal hearing and a normal CT scan of the temporal bone (Wen_2019). These reports do not provide unequivocal conclusions about association of the variant with Pendred Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV002503295 | SCV002814628 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome | 2022-03-09 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV003481131 | SCV004224062 | uncertain significance | not provided | 2023-02-08 | criteria provided, single submitter | clinical testing | PP3, PM1, PM2_supporting |