ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.358G>A (p.Glu120Lys)

gnomAD frequency: 0.00001  dbSNP: rs528216023
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518624 SCV000613515 uncertain significance not specified 2017-05-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587927 SCV000698249 uncertain significance not provided 2016-05-23 criteria provided, single submitter clinical testing Variant summary: The GJB2 c.358G>A (p.Glu120Lys) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index); however, functional studies had not been published at the time of classification to confirm these in silico predictions. This variant was found in 4/121052 control chromosomes at a frequency of 0.000033, which does not exceed the estimated maximal expected allele frequency of a pathogenic GJB2 variant (0.025). The variant was observed in 2 patients from the literature without significant evidence of causality (i.e. co-segregation data). The variant had not been classified by other clinical labs, but was reported as a pathogenic variant by one database without evidence to independently evaluate. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Counsyl RCV000666427 SCV000790718 uncertain significance Autosomal recessive nonsyndromic hearing loss 1A 2017-04-05 criteria provided, single submitter clinical testing
Invitae RCV000587927 SCV003281196 uncertain significance not provided 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 120 of the GJB2 protein (p.Glu120Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs528216023, ExAC 0.01%). This missense change has been observed in individual(s) with deafness (PMID: 17666888; Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 447444). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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.
Natera, Inc. RCV000666427 SCV001463375 uncertain significance Autosomal recessive nonsyndromic hearing loss 1A 2020-09-16 no assertion criteria provided clinical testing

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