NM_000883.4(IMPDH1):c.962C>T (p.Ala321Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 8, 2022
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:: RCV001560022.6

Allele description [Variation Report for NM_000883.4(IMPDH1):c.962C>T (p.Ala321Val)]

NM_000883.4(IMPDH1):c.962C>T (p.Ala321Val)

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.962C>T (p.Ala321Val)

HGVS:

NC_000007.14:g.128398526G>A
NG_009194.1:g.16457C>T
NM_000883.4:c.962C>TMANE SELECT
NM_001102605.2:c.932C>T
NM_001142573.2:c.707C>T
NM_001142574.2:c.692C>T
NM_001142575.2:c.632C>T
NM_001142576.2:c.863C>T
NM_001304521.2:c.755C>T
NM_183243.3:c.854C>T
NP_000874.2:p.Ala321Val
NP_001096075.1:p.Ala311Val
NP_001136045.1:p.Ala236Val
NP_001136046.1:p.Ala231Val
NP_001136047.1:p.Ala211Val
NP_001136048.1:p.Ala288Val
NP_001291450.1:p.Ala252Val
NP_899066.1:p.Ala285Val
NC_000007.13:g.128038580G>A
NM_000883.3:c.962C>T

Protein change:

A211V

Links:

dbSNP: rs1584728088

NCBI 1000 Genomes Browser:

rs1584728088

Molecular consequence:

NM_000883.4:c.962C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001102605.2:c.932C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142573.2:c.707C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142574.2:c.692C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142575.2:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142576.2:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304521.2:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_183243.3:c.854C>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
SCV001782353	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 3, 2020)	germline	clinical testing	Citation Link,
SCV003440111	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 8, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25698705, 30718709, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001782353

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 3, 2020)

germline

clinical testing

Citation Link,

SCV003440111

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 8, 2022)

germline

clinical testing

PubMed (3)
[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	yes	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

Targeted Next-Generation Sequencing Improves the Diagnosis of Autosomal Dominant Retinitis Pigmentosa in Spanish Patients.

Fernandez-San Jose P, Corton M, Blanco-Kelly F, Avila-Fernandez A, Lopez-Martinez MA, Sanchez-Navarro I, Sanchez-Alcudia R, Perez-Carro R, Zurita O, Sanchez-Bolivar N, Lopez-Molina MI, Garcia-Sandoval B, Riveiro-Alvarez R, Ayuso C.

Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2173-82. doi: 10.1167/iovs.14-16178.

PubMed [citation]

PMID:: 25698705

Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.

Jespersgaard C, Fang M, Bertelsen M, Dang X, Jensen H, Chen Y, Bech N, Dai L, Rosenberg T, Zhang J, Møller LB, Tümer Z, Brøndum-Nielsen K, Grønskov K.

Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.

PubMed [citation]

PMID:: 30718709
PMCID:: PMC6362094

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV001782353.1

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

Description

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25698705, 30718709, 26321861)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003440111.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 636038). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 25698705, 30718709). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 321 of the IMPDH1 protein (p.Ala321Val).

#	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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