NM_000883.4(IMPDH1):c.969G>T (p.Lys323Asn) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 6, 2021
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:: RCV001879212.6

Allele description [Variation Report for NM_000883.4(IMPDH1):c.969G>T (p.Lys323Asn)]

NM_000883.4(IMPDH1):c.969G>T (p.Lys323Asn)

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.969G>T (p.Lys323Asn)

HGVS:

NC_000007.14:g.128398519C>A
NG_009194.1:g.16464G>T
NM_000883.4:c.969G>TMANE SELECT
NM_001102605.2:c.939G>T
NM_001142573.2:c.714G>T
NM_001142574.2:c.699G>T
NM_001142575.2:c.639G>T
NM_001142576.2:c.870G>T
NM_001304521.2:c.762G>T
NM_183243.3:c.861G>T
NP_000874.2:p.Lys323Asn
NP_001096075.1:p.Lys313Asn
NP_001136045.1:p.Lys238Asn
NP_001136046.1:p.Lys233Asn
NP_001136047.1:p.Lys213Asn
NP_001136048.1:p.Lys290Asn
NP_001291450.1:p.Lys254Asn
NP_899066.1:p.Lys287Asn
NC_000007.13:g.128038573C>A

Protein change:

K213N

Links:

dbSNP: rs761583072

NCBI 1000 Genomes Browser:

rs761583072

Molecular consequence:

NM_000883.4:c.969G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001102605.2:c.939G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142573.2:c.714G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142574.2:c.699G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142575.2:c.639G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142576.2:c.870G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304521.2:c.762G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_183243.3:c.861G>T - 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
SCV002141888	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 6, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16038673, 28488341, 28559085, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002141888

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 6, 2021)

germline

clinical testing

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

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

Citations

PubMed

Screening for mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa.

Wada Y, Tada A, Itabashi T, Kawamura M, Sato H, Tamai M.

Am J Ophthalmol. 2005 Jul;140(1):163-5.

PubMed [citation]

PMID:: 16038673

Next-generation sequencing targeted disease panel in rod-cone retinal dystrophies in Māori and Polynesian reveals novel changes and a common founder mutation.

Vincent AL, Abeysekera N, van Bysterveldt KA, Oliver VF, Ellingford JM, Barton S, Black GC.

Clin Exp Ophthalmol. 2017 Dec;45(9):901-910. doi: 10.1111/ceo.12983. Epub 2017 Jun 13.

PubMed [citation]

PMID:: 28488341

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002141888.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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. This variant disrupts the p.Lys323 amino acid residue in IMPDH1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16038673, 28488341, 28559085, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with retinitis pigmentosa (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 323 of the IMPDH1 protein (p.Lys323Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine.

#	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: Sep 29, 2024

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