Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000667009 | SCV000791395 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 1A | 2017-05-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004768525 | SCV005380893 | uncertain significance | not specified | 2024-08-19 | criteria provided, single submitter | clinical testing | Variant summary: GJB2 c.278T>C (p.Met93Thr) results in a non-conservative amino acid change located in the Connexin, N-terminal domain (IPR013092) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251230 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.278T>C has been reported in the literature in the simple heterozygous state in at least 1 individual affected with Autosomal Recessive Non-Syndromic Hearing Loss (example, Putcha_2007), however this is an insufficient genotype for the reported inheritance pattern. These report(s) do not provide unequivocal conclusions about association of the variant with Autosomal Recessive Non-Syndromic Hearing Loss. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 17666888). ClinVar contains an entry for this variant (Variation ID: 551851). Based on the evidence outlined above, the variant was classified as uncertain significance. |