ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.550C>T (p.Arg184Trp) (rs998045226)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089546 SCV001244786 pathogenic Deafness, autosomal recessive 1A 2017-07-12 criteria provided, single submitter clinical testing The NM_004004.5(GJB2):c.550C>T missense variant identified in exon 2 of GJB2, is predicted to create a major amino acid change from an arginine to a tryptophan at amino acid position 184, NP_003995.2(GJB2):p.(Arg184Trp). The arginine at this position has high conservation (100 vertebrates, UCSC). In silico software predicts this variant to be disease causing. It is situated within the cysteine rich domain of theGJB2 protein. This variant has been observed in a population database at a frequency of 0.00001% (ExAC, GnomAD). This variant has been reported as a pathogenic variant in multiple patients with hearing loss (Deafness variation database, The Connexin-deafness homepage). Based on current information and in association with the NM_004004.5(GJB2):c.101T>C missense variant, this variant has been classified as PATHOGENIC. The presence of these two variants suggests a possible compound heterozygous mode of inheritance which is consistent with autosomal recessive deafness.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678887 SCV000805080 pathogenic Hearing loss 2006-11-10 no assertion criteria provided clinical testing
Hearing and Balance Clinic,First Affliiated Hospital of Kunming Medical University RCV001078465 SCV001190534 pathogenic Deafness, autosomal dominant 3a 2020-03-25 no assertion criteria provided clinical testing Arg184Trp variant in GJB2 has been found in a Chinese family with autosomal recessive inheritance hearing loss, segregated with the disease in the family members. The proband was homozygous of this mutation and the parents carried this variant equally. The proband has bilateral profound hearing loss and the parents have normal hearing .

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