NM_000883.4(IMPDH1):c.967A>G (p.Lys323Glu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 14, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000757408.8

Allele description [Variation Report for NM_000883.4(IMPDH1):c.967A>G (p.Lys323Glu)]

NM_000883.4(IMPDH1):c.967A>G (p.Lys323Glu)

Gene:

IMPDH1:inosine monophosphate dehydrogenase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_000883.4(IMPDH1):c.967A>G (p.Lys323Glu)

HGVS:

NC_000007.14:g.128398521T>C
NG_009194.1:g.16462A>G
NM_000883.4:c.967A>GMANE SELECT
NM_001102605.2:c.937A>G
NM_001142573.2:c.712A>G
NM_001142574.2:c.697A>G
NM_001142575.2:c.637A>G
NM_001142576.2:c.868A>G
NM_001304521.2:c.760A>G
NM_183243.3:c.859A>G
NP_000874.2:p.Lys323Glu
NP_001096075.1:p.Lys313Glu
NP_001136045.1:p.Lys238Glu
NP_001136046.1:p.Lys233Glu
NP_001136047.1:p.Lys213Glu
NP_001136048.1:p.Lys290Glu
NP_001291450.1:p.Lys254Glu
NP_899066.1:p.Lys287Glu
NC_000007.13:g.128038575T>C
NM_000883.3:c.967A>G

Protein change:

K213E

Links:

dbSNP: rs1562989913

NCBI 1000 Genomes Browser:

rs1562989913

Molecular consequence:

NM_000883.4:c.967A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001102605.2:c.937A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142573.2:c.712A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142574.2:c.697A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142575.2:c.637A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142576.2:c.868A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001304521.2:c.760A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_183243.3:c.859A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000885616	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (May 14, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000885616

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(May 14, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885616.1

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

Description

The IMPDH1 c.967A>G; p.Lys323Glu variant, also known as Lys238Glu, is reported in the medical literature in a small family with autosomal dominant RP (Wada 2005a). Additionally, another variant in the same codon, p.Lys323Arg, is reported in at least two individuals with autosomal dominant RP (Pradan 2009, Vincent 2017, Wada 2005b). The p.Lys323Glu variant is not reported in the ClinVar database, and is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The lysine at this position is conserved across species but computational algorithms predict this variant is tolerated (AlignGVGD, SIFT). Considering available information, the clinical significance of this variant cannot be determined with certainty. Pathogenic variants in IMPDH1 are associated with autosomal dominant retinitis pigmentosa (RP, MIM: 180105). References: Pradhan M et al. An audit of genetic testing in diagnosis of inherited retinal disorders: a prerequisite for gene-specific intervention. Clin Exp Ophthalmol. 2009 Sep;37(7):703-11. Vincent AL et al. Next-generation sequencing targeted disease panel in rod-cone retinal dystrophies in Maori and Polynesian reveals novel changes and a common founder mutation. Clin Exp Ophthalmol. 2017 Dec;45(9):901-910. Wada Y et al a. Screen of the IMPDH1 gene among patients with dominant retinitis pigmentosa and clinical features associated with the most common mutation, Asp226Asn. Invest Ophthalmol Vis Sci. 2005 May;46(5):1735-41. Wada Y et al b. Screening for mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa. Am J Ophthalmol. 2005 Jul;140(1):163-5.

#	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

Last Updated: Nov 3, 2024

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