Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000175011 | SCV000226430 | uncertain significance | not provided | 2015-01-22 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000415063 | SCV000492633 | uncertain significance | Hearing impairment | 2015-03-27 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001785491 | SCV002027016 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 4 | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001785490 | SCV002027017 | uncertain significance | Pendred syndrome | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488425 | SCV004241046 | uncertain significance | not specified | 2023-12-13 | criteria provided, single submitter | clinical testing | Variant summary: SLC26A4 c.1730T>C (p.Val577Ala) results in a non-conservative amino acid change located in the STAS domain of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251110 control chromosomes. c.1730T>C has been reported in the literature in individuals affected with suspected Pendred Syndrome and hearing loss (Tesolin_2021, Roesch_2018, Likar_2018). These reports do not provide unequivocal conclusions about association of the variant with Pendred Syndrome. A functional study with variant-transfected cells showed severe loss in ion transport function, complete retention in the ER and dramatic reduction of expression (Roesch_2018). The following publications have been ascertained in the context of this evaluation (PMID: 29293505, 29320412, 34680964). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |