ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.9466A>G (p.Ile3156Val) (rs372484022)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039661 SCV000063350 uncertain significance not specified 2012-05-07 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ile3156Val vari ant (GPR98) has not been reported in the literature or in SNP databases nor prev iously identified by our laboratory. Computational analyses (biochemical amino a cid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide str ong support for or against an impact to the protein; however, Isoleucine (Ile) a t position 3156 is replaced by Val (Valine) in zebrafish suggesting the variant is more likely benign. In summary, the clinical significance of this variant can not be determined with certainty at this time, though we would lean towards a mo re likely benign role.
Invitae RCV001358284 SCV001650125 likely benign not provided 2020-10-07 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358284 SCV001553973 likely benign not provided no assertion criteria provided clinical testing The ADGRV1 p.Ile3156Val variant was identified in 1 of 190 proband chromosomes (frequency: 0.00526) from individuals or families with myoclonic seizures and was not identified in 1056 control chromosomes from healthy individuals (Myers_2018_PMID:29266188). The variant was also identified in dbSNP (ID: rs372484022) and in ClinVar (classifed as a VUS by Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine). The variant was not identified in Cosmic or LOVD 3.0. The variant was identified in control databases in 69 of 279132 chromosomes (1 homozygous) at a frequency of 0.000247 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 57 of 30568 chromosomes (freq: 0.001865), Latino in 3 of 35298 chromosomes (freq: 0.000085), European (non-Finnish) in 7 of 127064 chromosomes (freq: 0.000055), African in 1 of 24196 chromosomes (freq: 0.000041), European (Finnish) in 1 of 25022 chromosomes (freq: 0.00004), while the variant was not observed in the Ashkenazi Jewish, East Asian, and Other populations. The p.Ile3156 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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