Total submissions: 5
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, |
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, |
RCV000666427 | SCV001463375 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 1A | 2020-09-16 | no assertion criteria provided | clinical testing |