ClinVar Miner

Submissions for variant NM_001080476.3(GRXCR1):c.594_597dup (p.Val200fs)

dbSNP: rs1553941938
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000603853 SCV000711950 pathogenic Rare genetic deafness 2016-05-01 criteria provided, single submitter clinical testing The p.Val200fs variant in GRXCR1 has been identified in the homozygous state by our laboratory in 1 individual with hearing loss and segregated in an affected s ibling (this family). This variant was absent from large population studies, tho ugh the ability of these studies to accurately detect indels may be limited. The p.Val200fs variant is predicted to cause a frameshift, which alters the protein ?s amino acid sequence beginning at position 200 and leads to a premature termin ation codon 6 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function (LoF) variants in the GRXCR1 have been reported in individuals with hearing loss, and a mouse model study sup ports LoF as a disease mechanism (Odeh 2010). In summary, the p.Val200fs variant meets our criteria to be classified as pathogenic for hearing loss in an autoso mal recessive manner based on the predicted impact of the variant.

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