ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.12625G>A (p.Glu4209Lys)

gnomAD frequency: 0.00001  dbSNP: rs141943290
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Total submissions: 5
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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 RCV000610578 SCV000711232 uncertain significance not specified 2016-10-06 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Glu4209Lys va riant in USH2A has not been previously reported in individuals with hearing loss or Usher syndrome. It has been identified in 12/66294 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 141943290); however, this frequency is not high enough to rule out a pathogenic role. The glutamic acid residue (Glu) at position 4209 is not conserved across species, with two mammals (prairie vole and golden hamster) having a lysine (Lys ) at this position. Additional computational predictions suggest that this varia nt may not impact the protein. In summary, while the clinical significance of th is variant is uncertain, these data suggest that it is more likely to be benign.
Invitae RCV001454312 SCV001658035 likely benign not provided 2023-12-02 criteria provided, single submitter clinical testing
GeneDx RCV001454312 SCV002584208 uncertain significance not provided 2022-04-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002532735 SCV003697703 uncertain significance Inborn genetic diseases 2022-04-25 criteria provided, single submitter clinical testing The c.12625G>A (p.E4209K) alteration is located in exon 63 (coding exon 62) of the USH2A gene. This alteration results from a G to A substitution at nucleotide position 12625, causing the glutamic acid (E) at amino acid position 4209 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001272950 SCV001455401 uncertain significance Usher syndrome type 2A 2019-11-11 no assertion criteria provided clinical testing

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