NM_032119.4(ADGRV1):c.13496G>A (p.Arg4499His) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(3) (Last evaluated: Oct 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000724676.6

Allele description [Variation Report for NM_032119.4(ADGRV1):c.13496G>A (p.Arg4499His)]

NM_032119.4(ADGRV1):c.13496G>A (p.Arg4499His)

Gene:
ADGRV1:adhesion G protein-coupled receptor V1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q14.3
Genomic location:
Preferred name:
NM_032119.4(ADGRV1):c.13496G>A (p.Arg4499His)
HGVS:
  • NC_000005.10:g.90783900G>A
  • NG_007083.2:g.259557G>A
  • NM_032119.4:c.13496G>AMANE SELECT
  • NP_115495.3:p.Arg4499His
  • LRG_1095t1:c.13496G>A
  • LRG_1095:g.259557G>A
  • LRG_1095p1:p.Arg4499His
  • NC_000005.9:g.90079717G>A
  • NM_032119.3:c.13496G>A
  • NR_003149.2:n.13512G>A
Protein change:
R4499H
Links:
dbSNP: rs375122809
NCBI 1000 Genomes Browser:
rs375122809
Molecular consequence:
  • NM_032119.4:c.13496G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_003149.2:n.13512G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
2

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000331854EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Aug 30, 2018)
germlineclinical testing

Citation Link,

SCV001142921Athena Diagnostics Inccriteria provided, single submitter
Uncertain significance
(May 14, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001210983Invitaecriteria provided, single submitter
Uncertain significance
(Oct 15, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001766733GeneDxcriteria provided, single submitter
Likely benign
(Jan 28, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000331854.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not providednot providednot provided

From Athena Diagnostics Inc, SCV001142921.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001210983.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with histidine at codon 4499 of the ADGRV1 protein (p.Arg4499His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs375122809, ExAC 0.08%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 179571). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0. The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001766733.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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