ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.31_68del (p.Gly11fs) (rs397516873)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037837 SCV000061499 pathogenic Rare genetic deafness 2012-04-17 criteria provided, single submitter clinical testing The Gly11fs variant in GJB2 has been reported in one individual with hearing los s (Denoyelle 1997). This frameshift variant is predicted to alter the protein?s amino acid sequence beginning at position 11 and lead to a premature termination codon 24 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LMM).
Counsyl RCV000411009 SCV000487542 likely pathogenic Deafness, autosomal dominant 3a 2016-03-14 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000517627 SCV000613511 pathogenic not provided 2017-03-07 criteria provided, single submitter clinical testing
GeneDx RCV000517627 SCV001167921 pathogenic not provided 2018-06-18 criteria provided, single submitter clinical testing The c.31_68del38 variant in the GJB2 gene has been reported previously in association with hearing loss (Snoeckx et al., 2005; Dodson et al., 2011; Beck et al., 2014). The deletion causes a frameshift starting with codon Glycine 11, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 24 of the new reading frame, denoted p.Gly11LeufsX24. This variant is predicted to cause loss of normal protein function through protein truncation. The variant is observed in 5/110262 (0.0045%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001527052 SCV001737887 pathogenic Nonsyndromic hearing loss and deafness 2021-06-09 criteria provided, single submitter clinical testing Variant summary: GJB2 c.31_68del38 (p.Gly11LeufsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 250064 control chromosomes. c.31_68del38 has been reported in the literature in multiple individuals affected with Non-Syndromic Hearing Loss (e.g. Denoyelle_1997, Janecke_2002, Dodson_2011, Beck_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories cited the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Counsyl RCV000409896 SCV000487541 likely pathogenic Deafness, autosomal recessive 1A 2016-03-14 no assertion criteria provided clinical testing

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