NM_000379.4(XDH):c.3886C>T (p.Arg1296Trp) AND Hereditary xanthinuria type 1

Germline classification:: Benign (3 submissions)
Last evaluated:: Dec 5, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001142398.7

Allele description [Variation Report for NM_000379.4(XDH):c.3886C>T (p.Arg1296Trp)]

NM_000379.4(XDH):c.3886C>T (p.Arg1296Trp)

Gene:

XDH:xanthine dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.1

Genomic location:

Preferred name:

NM_000379.4(XDH):c.3886C>T (p.Arg1296Trp)

HGVS:

NC_000002.12:g.31337706G>A
NG_008871.2:g.82040C>T
NM_000379.4:c.3886C>TMANE SELECT
NP_000370.2:p.Arg1296Trp
NC_000002.11:g.31560572G>A
NG_008871.1:g.82040C>T
NM_000379.3:c.3886C>T

Protein change:

R1296W

Links:

dbSNP: rs45564939

NCBI 1000 Genomes Browser:

rs45564939

Molecular consequence:

NM_000379.4:c.3886C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary xanthinuria type 1 (XAN1)
Synonyms:: Xanthinuria type 1; XDH deficiency
Identifiers:: MONDO: MONDO:0010209; MedGen: C0268118; Orphanet: 3467; OMIM: 278300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001302833	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26283345, 22981351 Citation Link,
SCV001435131	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	research	PubMed (1) [See all records that cite this PMID]
SCV002513951	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Dec 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001302833

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001435131

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign

germline

research

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

SCV002513951

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Dec 5, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Plasma metabolomic profiles enhance precision medicine for volunteers of normal health.

Guo L, Milburn MV, Ryals JA, Lonergan SC, Mitchell MW, Wulff JE, Alexander DC, Evans AM, Bridgewater B, Miller L, Gonzalez-Garay ML, Caskey CT.

Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):E4901-10. doi: 10.1073/pnas.1508425112. Epub 2015 Aug 17.

PubMed [citation]

PMID:: 26283345
PMCID:: PMC4568216

Identification of a xanthinuria type I case with mutations of xanthine dehydrogenase in an Afghan child.

Nakamura M, Yuichiro Y, Sass JO, Tomohiro M, Schwab KO, Takeshi N, Tatsuo H, Ichida K.

Clin Chim Acta. 2012 Dec 24;414:158-60. doi: 10.1016/j.cca.2012.08.011. Epub 2012 Aug 17.

PubMed [citation]

PMID:: 22981351

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001302833.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001435131.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

Description

The p.Arg1296Trp variant in XDH has been identified in an Afghan individual with xanthinuria and two other variants (a frameshift variant confirmed in trans with a missense variant with functional evidence supporting pathogenicity) in XDH (PMID: 22981351). This variant has been identified in >2% of European (Finnish) chromosomes and 15 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Arg1296Trp variant may not impact protein function (PMID: 22981351). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autosomal recessive xanthinuria.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002513951.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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