NM_173477.5(USH1G):c.83C>T (p.Pro28Leu) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: May 12, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000432648.8

Allele description [Variation Report for NM_173477.5(USH1G):c.83C>T (p.Pro28Leu)]

NM_173477.5(USH1G):c.83C>T (p.Pro28Leu)

Genes:
USH1G:USH1 protein network component sans [Gene - OMIM - HGNC]
OTOP2:otopetrin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q25.1
Genomic location:
Preferred name:
NM_173477.5(USH1G):c.83C>T (p.Pro28Leu)
HGVS:
  • NC_000017.11:g.74922991G>A
  • NG_007882.2:g.5273C>T
  • NG_033062.1:g.3717G>A
  • NG_033062.2:g.3717G>A
  • NM_001282489.3:c.-174C>T
  • NM_173477.5:c.83C>TMANE SELECT
  • NP_775748.2:p.Pro28Leu
  • LRG_1416t1:c.83C>T
  • LRG_1416:g.5273C>T
  • LRG_1416p1:p.Pro28Leu
  • NC_000017.10:g.72919086G>A
  • NM_173477.2:c.83C>T
  • NM_173477.4:c.83C>T
  • c.83C>T
Protein change:
P28L
Links:
dbSNP: rs145448362
NCBI 1000 Genomes Browser:
rs145448362
Molecular consequence:
  • NM_001282489.3:c.-174C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_173477.5:c.83C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000510711Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinicscriteria provided, single submitter
Uncertain Significance
(Jan 25, 2017)
germlineclinical testing

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

SCV000970667GeneDxcriteria provided, single submitter
Likely benign
(May 12, 2020)
germlineclinical testing

Citation Link,

SCV001234492Invitaecriteria provided, single submitter
Uncertain significance
(Jan 3, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001953701Human Genetics - Radboudumc,Radboudumc - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedUncertain significancegermlineclinical testing

SCV001975071Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedUncertain significancegermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Diagnostic exome sequencing in 266 Dutch patients with visual impairment.

Haer-Wigman L, van Zelst-Stams WA, Pfundt R, van den Born LI, Klaver CC, Verheij JB, Hoyng CB, Breuning MH, Boon CJ, Kievit AJ, Verhoeven VJ, Pott JW, Sallevelt SC, van Hagen JM, Plomp AS, Kroes HY, Lelieveld SH, Hehir-Kwa JY, Castelein S, Nelen M, Scheffer H, Lugtenberg D, et al.

Eur J Hum Genet. 2017 May;25(5):591-599. doi: 10.1038/ejhg.2017.9. Epub 2017 Feb 22.

PubMed [citation]
PMID:
28224992
PMCID:
PMC5437915
See all PubMed Citations (5)

Details of each submission

From Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000510711.1

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

Description

Converted during submission to Uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot provided0.001637not providednot provided

From GeneDx, SCV000970667.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is associated with the following publications: (PMID: 17896313, 28224992)

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

From Invitae, SCV001234492.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces proline with leucine at codon 28 of the USH1G protein (p.Pro28Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs145448362, ExAC 0.2%). This variant has been observed in individuals affected with Usher syndrome or retinitis pigmentosa (PMID: 28224992, 17896313, 22135276). ClinVar contains an entry for this variant (Variation ID: 48139). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 Human Genetics - Radboudumc,Radboudumc - VKGL Data-share Consensus, SCV001953701.1

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001975071.1

#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: Oct 6, 2021

Support Center