Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000214320 | SCV000271823 | uncertain significance | not specified | 2015-04-20 | criteria provided, single submitter | clinical testing | The p.Val2927Ile variant in GPR98 has not been previously reported in individual s with hearing loss, but has been identified in 7/66708 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 547397177). Computational prediction tools and conservation analyses suggest tha t the p.Val2927Ile variant may not impact the protein, though this information i s not predictive enough to rule out pathogenicity. In summary, the clinical sign ificance of the p.Val2927Ile variant is uncertain. |
| Gene |
RCV000767096 | SCV000621055 | uncertain significance | not provided | 2017-09-22 | criteria provided, single submitter | clinical testing | The V2927I variant in the ADGRV1 gene has been reported previously in an individual with retinitis pigmentosa, however a second variant was not identified (Bravo-Gil et al., 2017). The V2927I variant is observed in 7/66708 (0.01%) alleles from individuals of non-Finnish European background, in the ExAC dataset (Lek et al., 2016). The V2927I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V2927I as a variant of uncertain significance. |
| Labcorp Genetics |
RCV000767096 | SCV001420088 | likely benign | not provided | 2024-12-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000214320 | SCV003844726 | uncertain significance | not specified | 2023-02-14 | criteria provided, single submitter | clinical testing | Variant summary: ADGRV1 c.8779G>A (p.Val2927Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.8e-05 in 248910 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ADGRV1 causing Usher Syndrome (6.8e-05 vs 0.0054), allowing no conclusion about variant significance. c.8779G>A has been reported in the literature in one heterozygous individual affected with retinitis pigmentosa, although a second ADGRV1 variant was not detected (Bravo-Gil_2017), as well as a compound heterozygous individual with Usher syndrome, although a second truncating ADGRV1 was identified in cis (Candelo_2021). These reports therefore do not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) have cited the variant, with two submitters classifying the variant as uncertain significance and one submitter classifying it as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |