NM_001009944.3(PKD1):c.971G>T (p.Arg324Leu) AND Polycystic kidney disease, adult type

Clinical significance:Conflicting interpretations of pathogenicity, Benign(1);Uncertain significance(1) (Last evaluated: Apr 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000008688.7

Allele description [Variation Report for NM_001009944.3(PKD1):c.971G>T (p.Arg324Leu)]

NM_001009944.3(PKD1):c.971G>T (p.Arg324Leu)

Gene:
PKD1:polycystin 1, transient receptor potential channel interacting [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_001009944.3(PKD1):c.971G>T (p.Arg324Leu)
HGVS:
  • NC_000016.10:g.2118021C>A
  • NG_008617.1:g.22878G>T
  • NM_000296.4:c.971G>T
  • NM_001009944.3:c.971G>TMANE SELECT
  • NP_000287.4:p.Arg324Leu
  • NP_001009944.3:p.Arg324Leu
  • NC_000016.9:g.2168022C>A
  • NM_000296.3:c.971G>T
  • NM_001009944.2:c.971G>T
  • P98161:p.Arg324Leu
Protein change:
R324L; ARG324LEU
Links:
UniProtKB: P98161#VAR_010085; OMIM: 601313.0011; dbSNP: rs199476099
NCBI 1000 Genomes Browser:
rs199476099
Molecular consequence:
  • NM_000296.4:c.971G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001009944.3:c.971G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Polycystic kidney disease, adult type (PKD1)
Synonyms:
Polycystic Kidney, Autosomal Dominant; POLYCYSTIC KIDNEY DISEASE, ADULT, TYPE I; Polycystic kidney disease 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008263; MedGen: C3149841; OMIM: 173900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000028897OMIMno assertion criteria providedPathogenic
(Jul 1, 1999)
germlineliterature only

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

SCV000884320ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Benign
(Apr 19, 2019)
germlineclinical testing

Citation Link,

SCV001142453Reproductive Health Research and Development,BGI Genomicsno assertion criteria providedUncertain significance
(Jan 6, 2020)
germlinecuration

SCV001370129Centre for Mendelian Genomics,University Medical Centre Ljubljanacriteria provided, single submitter
Uncertain significance
(Jan 1, 2016)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR.

Thomas R, McConnell R, Whittacker J, Kirkpatrick P, Bradley J, Sandford R.

Am J Hum Genet. 1999 Jul;65(1):39-49.

PubMed [citation]
PMID:
10364515
PMCID:
PMC1378073

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

Details of each submission

From OMIM, SCV000028897.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

One of 7 unique mutations identified by Thomas et al. (1999) by long-range PCR and direct sequencing of the PKD1 gene in patients with polycystic kidney disease (PKD1; 173900) was an arg324-to-leu (R324L) mutation in exon 5.

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884320.2

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

From Reproductive Health Research and Development,BGI Genomics, SCV001142453.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_001009944.2:c.971G>T in the PKD1 gene has an allele frequency of 0.006 in European (Finnish) subpopulation in the gnomAD database. This variant has been detected in a individual with autosomal dominant polycystic kidney disease (PMID: 10364515). Benign computational verdict because benign predictions from DEOGEN2, EIGEN, FATHMM-MKL, PrimateAI and SIFT. As a dominant inheritance manner, a total of 626 allleles was detected in gnomAD database which is a evidence to against its pathogenicity, although the adult-onset should be considered. We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PP4, BP4.

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

From Centre for Mendelian Genomics,University Medical Centre Ljubljana, SCV001370129.2

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

Description

This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PS1,PP3,PP4,BP6,BS2.

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

Last Updated: Nov 20, 2021

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