ClinVar Miner

Submissions for variant NM_001110219.3(GJB6):c.518C>T (p.Pro173Leu)

gnomAD frequency: 0.00006  dbSNP: rs200480676
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001244269 SCV001417477 uncertain significance Autosomal recessive nonsyndromic hearing loss 1A; Autosomal recessive nonsyndromic hearing loss 1B; Autosomal dominant nonsyndromic hearing loss 3B; Hidrotic ectodermal dysplasia syndrome 2019-10-14 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GJB6-related conditions. This variant is present in population databases (rs200480676, ExAC 0.009%). This sequence change replaces proline with leucine at codon 173 of the GJB6 protein (p.Pro173Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
Ambry Genetics RCV002568581 SCV003577660 uncertain significance Inborn genetic diseases 2022-12-16 criteria provided, single submitter clinical testing The c.518C>T (p.P173L) alteration is located in exon 3 (coding exon 1) of the GJB6 gene. This alteration results from a C to T substitution at nucleotide position 518, causing the proline (P) at amino acid position 173 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003156327 SCV003845536 uncertain significance not provided 2023-03-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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.