ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.17G>T (p.Gly6Val)

gnomAD frequency: 0.00010  dbSNP: rs111033423
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036459 SCV000060114 benign not specified 2017-04-25 criteria provided, single submitter clinical testing The p.Gly6Val variant in exon 2 of SLC26A4: This variant is not expected to have clinical significance because it has been identified in 1.6% (398/25068) of Sou th Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.b roadinstitute.org; dbSNP rs111033423).
Counsyl RCV000169379 SCV000220767 likely benign Pendred syndrome 2014-10-17 criteria provided, single submitter literature only
GeneDx RCV000757777 SCV000731038 benign not provided 2019-09-30 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28444304, 20597900, 25991456, 26188157, 20601923)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757777 SCV000886132 likely benign not provided 2018-01-23 criteria provided, single submitter clinical testing The c.17G>T; p.Gly6Val variant (rs111033423, ClinVar variant ID 43524) has been reported in patients with hearing loss (Pourova 2010, Tang 2015) and congenital hypothyroidism (de Filippis 2017); however, it was also detected at a similar frequency in a control population (Pourova 2010). This variant is listed in the genome Aggregation Database (gnomAD) with a South Asian population frequency of 1.6% (identified on 398 out of 25,068 chromosomes, including 6 homozygotes). The glycine at position 6 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Gly6Val variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the p.Gly6Val variant is likely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV000757777 SCV001067872 benign not provided 2024-01-27 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000169379 SCV001326716 benign Pendred syndrome 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina RCV001164583 SCV001326717 uncertain significance Autosomal recessive nonsyndromic hearing loss 4 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab RCV001164583 SCV002027117 likely benign Autosomal recessive nonsyndromic hearing loss 4 2021-09-05 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000169379 SCV002027228 likely benign Pendred syndrome 2021-09-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036459 SCV002570598 benign not specified 2022-07-12 criteria provided, single submitter clinical testing Variant summary: SLC26A4 c.17G>T (p.Gly6Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0025 in 177348 control chromosomes, predominantly at a frequency of 0.016 within the South Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 5 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC26A4 causing Pendred Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Eight ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1), likely benign (n=2) and benign (n=5). Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc. RCV000169379 SCV002079957 benign Pendred syndrome 2019-11-11 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.