This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 343 of the NLRP12 protein (p.Arg343Trp). This variant is present in population databases (rs112159191, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 440985). 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. 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.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Uncertain significance
- Review status:
- criteria provided, single submitter
- Submissions:
- 2
- First in ClinVar:
- Oct 16, 2017
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Sep 7, 2022
- Accession:
- VCV000440985.4
- Variation ID:
- 440985
- Description:
- single nucleotide variant
Help
NM_144687.4(NLRP12):c.1027C>T (p.Arg343Trp)
- Allele ID
- 434676
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 19q13.42
- Genomic location
- 19: 53810632 (GRCh38) GRCh38 UCSC
- 19: 54313886 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_144687.4:c.1027C>T MANE Select NP_653288.1:p.Arg343Trp missense NM_001277126.2:c.1027C>T NP_001264055.1:p.Arg343Trp missense NM_001277129.1:c.1027C>T NP_001264058.1:p.Arg343Trp missense NC_000019.10:g.53810632G>A NC_000019.9:g.54313886G>A NG_008651.2:g.18763C>T LRG_181:g.18763C>T LRG_181t1:c.1027C>T LRG_181p1:p.Arg343Trp LRG_181t2:c.1027C>T LRG_181p2:p.Arg343Trp - Protein change
- R343W
- Other names
- -
- Canonical SPDI
- NC_000019.10:53810631:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- The Genome Aggregation Database (gnomAD) 0.00006
- Trans-Omics for Precision Medicine (TOPMed) 0.00002
- Links
- ClinGen: CA9639538
- dbSNP: rs112159191
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| not provided | 1 | no assertion provided | - | RCV000509371.1 | |
| Uncertain significance | 1 | criteria provided, single submitter | Sep 7, 2022 | RCV000819856.3 |
Clinical features observed in individuals with this variant
- Tall stature
- Growth hormone excess
- Growth hormone deficiency
- Failure to thrive
- Short stature
- Hemihypertrophy
- Obesity
- Overgrowth
- Abnormality of the parathyroid physiology
- Hyperthyroidism
- Goiter
- Adrenal hyperplasia
- Hypogonadism
- Precocious puberty
- Diabetes insipidus
- Delayed puberty
- Type I diabetes mellitus
- Type II diabetes mellitus
- Oral-pharyngeal dysphagia
- Abnormality of the neck
- Abnormality of the mouth
- Abnormality of the oral cavity
- Abnormality of the optic nerve
- Hypermetropia
- Myopia
- Abnormality of vision
- Abnormality of eye movement
- Vertigo
- Tinnitus
- Sensorineural hearing impairment
- Abnormality of movement
- Memory impairment
- Abnormality of coordination
- Cognitive impairment
- Anxiety
- Autistic behavior
- Hyperpigmentation of the skin
- Multiple cafe-au-lait spots
- Joint hypermobility
- Abnormality of the curvature of the vertebral column
- Abnormality of muscle physiology
- Hypercholesterolemia
- Hypertension
- Abnormality of cardiovascular system morphology
- Syncope
- Cardiomyopathy
- Abnormal EKG
- Arrhythmia
- Asthma
- Abnormality of the intestine
- Gastrointestinal dysmotility
- Abnormality of the liver
- Abnormality of the stomach
- Abnormality of esophagus morphology
- Feeding difficulties
- Abnormality of urine homeostasis
- Abnormal renal morphology
- Abnormality of the bladder
- Rheumatoid arthritis
- Recurrent infections
- Abnormal inflammatory response
- Autoimmunity
- Abnormality of leukocytes
- Abnormality of erythrocytes
- Bleeding with minor or no trauma
- Abnormality of blood and blood-forming tissues
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Sep 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000960539.3
First in ClinVar: Aug 14, 2019 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 343 of the NLRP12 protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 343 of the NLRP12 protein (p.Arg343Trp). This variant is present in population databases (rs112159191, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 440985). 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. 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. (less)
|
|
|
not provided
(-)
|
no assertion provided
Method: phenotyping only
|
Affected status: unknown
Allele origin:
paternal
|
GenomeConnect, ClinGen
Accession: SCV000607009.1
First in ClinVar: Oct 16, 2017 Last updated: Oct 16, 2017 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Tall stature (present) , Growth hormone excess (present) , Growth hormone deficiency (present) , Failure to thrive (present) , Short stature (present) , Hemihypertrophy (present) … (more)
Tall stature (present) , Growth hormone excess (present) , Growth hormone deficiency (present) , Failure to thrive (present) , Short stature (present) , Hemihypertrophy (present) , Obesity (present) , Overgrowth (present) , Abnormality of the parathyroid physiology (present) , Hyperthyroidism (present) , Goiter (present) , Adrenal hyperplasia (present) , Hypogonadism (present) , Precocious puberty (present) , Diabetes insipidus (present) , Delayed puberty (present) , Type I diabetes mellitus (present) , Type II diabetes mellitus (present) , Oral-pharyngeal dysphagia (present) , Abnormality of the neck (present) , Abnormality of the mouth (present) , Abnormality of the oral cavity (present) , Abnormality of the optic nerve (present) , Hypermetropia (present) , Myopia (present) , Abnormality of vision (present) , Abnormality of eye movement (present) , Vertigo (present) , Tinnitus (present) , Sensorineural hearing impairment (present) , Abnormality of movement (present) , Memory impairment (present) , Abnormality of coordination (present) , Cognitive impairment (present) , Anxiety (present) , Autistic behavior (present) , Hyperpigmentation of the skin (present) , Multiple cafe-au-lait spots (present) , Joint hypermobility (present) , Abnormality of the curvature of the vertebral column (present) , Abnormality of muscle physiology (present) , Hypercholesterolemia (present) , Hypertension (present) , Abnormality of cardiovascular system morphology (present) , Syncope (present) , Cardiomyopathy (present) , Abnormal EKG (present) , Arrhythmia (present) , Asthma (present) , Abnormality of the intestine (present) , Gastrointestinal dysmotility (present) , Abnormality of the liver (present) , Abnormality of the stomach (present) , Abnormality of esophagus morphology (present) , Feeding difficulties (present) , Abnormality of urine homeostasis (present) , Abnormal renal morphology (present) , Abnormality of the bladder (present) , Rheumatoid arthritis (present) , Recurrent infections (present) , Abnormal inflammatory response (present) , Autoimmunity (present) , Abnormality of leukocytes (present) , Abnormality of erythrocytes (present) , Bleeding with minor or no trauma (present) , Abnormality of blood and blood-forming tissues (present) (less)
Indication for testing: Diagnostic
Age: 40-49 years
Sex: female
Method: Sanger Sequencing
Testing laboratory: GeneDx
Date variant was reported to submitter: 2016-09-09
Testing laboratory interpretation: Uncertain significance
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs112159191...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Feb 07, 2023