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NM_020975.6(RET):c.341G>A (p.Arg114His) AND Congenital central hypoventilation

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 1, 2002
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000014974.35

Allele description [Variation Report for NM_020975.6(RET):c.341G>A (p.Arg114His)]

NM_020975.6(RET):c.341G>A (p.Arg114His)

Gene:
RET:ret proto-oncogene [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q11.21
Genomic location:
Preferred name:
NM_020975.6(RET):c.341G>A (p.Arg114His)
HGVS:
  • NC_000010.11:g.43102345G>A
  • NG_007489.1:g.30277G>A
  • NM_000323.2:c.341G>A
  • NM_001406743.1:c.341G>A
  • NM_001406744.1:c.341G>A
  • NM_001406759.1:c.341G>A
  • NM_001406760.1:c.341G>A
  • NM_001406763.1:c.341G>A
  • NM_001406765.1:c.341G>A
  • NM_001406769.1:c.341G>A
  • NM_001406771.1:c.341G>A
  • NM_001406772.1:c.341G>A
  • NM_001406773.1:c.341G>A
  • NM_001406779.1:c.341G>A
  • NM_001406780.1:c.341G>A
  • NM_001406781.1:c.341G>A
  • NM_001406782.1:c.341G>A
  • NM_001406785.1:c.341G>A
  • NM_001406787.1:c.341G>A
  • NM_020629.2:c.341G>A
  • NM_020630.7:c.341G>A
  • NM_020975.6:c.341G>AMANE SELECT
  • NP_000314.1:p.Arg114His
  • NP_001393672.1:p.Arg114His
  • NP_001393673.1:p.Arg114His
  • NP_001393688.1:p.Arg114His
  • NP_001393689.1:p.Arg114His
  • NP_001393692.1:p.Arg114His
  • NP_001393694.1:p.Arg114His
  • NP_001393698.1:p.Arg114His
  • NP_001393700.1:p.Arg114His
  • NP_001393701.1:p.Arg114His
  • NP_001393702.1:p.Arg114His
  • NP_001393708.1:p.Arg114His
  • NP_001393709.1:p.Arg114His
  • NP_001393710.1:p.Arg114His
  • NP_001393711.1:p.Arg114His
  • NP_001393714.1:p.Arg114His
  • NP_001393716.1:p.Arg114His
  • NP_065680.1:p.Arg114His
  • NP_065681.1:p.Arg114His
  • NP_065681.1:p.Arg114His
  • NP_065681.1:p.Arg114His
  • NP_066124.1:p.Arg114His
  • NP_066124.1:p.Arg114His
  • LRG_518t1:c.341G>A
  • LRG_518t2:c.341G>A
  • LRG_518:g.30277G>A
  • LRG_518p1:p.Arg114His
  • LRG_518p2:p.Arg114His
  • NC_000010.10:g.43597793G>A
  • NM_020630.4:c.341G>A
  • NM_020630.6:c.341G>A
  • NM_020975.4:c.341G>A
  • P07949:p.Arg114His
  • p.R114H
Protein change:
R114H; ARG114HIS
Links:
UniProtKB: P07949#VAR_018154; OMIM: 164761.0045; dbSNP: rs76397662
NCBI 1000 Genomes Browser:
rs76397662
Molecular consequence:
  • NM_000323.2:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406743.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406744.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406759.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406760.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406763.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406765.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406769.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406771.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406772.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406773.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406779.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406780.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406781.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406782.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406785.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406787.1:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020629.2:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020630.7:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020975.6:c.341G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital central hypoventilation
Synonyms:
Idiopathic congenital central alveolar hypoventilation; Congenital failure of autonomic control; Primary alveolar hypoventilation; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0800031; MedGen: C1275808; Orphanet: 661; Orphanet: 99803; OMIM: PS209880

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000035230OMIM
no assertion criteria provided
Uncertain significance
(Apr 1, 2002) 		germlineliterature only

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

Hamosh, A. Personal Communication. 2021. Baltimore, Md.

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Congenital central hypoventilation syndrome: a novel mutation of the RET gene in an isolated case.

Kanai M, Numakura C, Sasaki A, Shirahata E, Akaba K, Hashimoto M, Hasegawa H, Shirasawa S, Hayasaka K.

Tohoku J Exp Med. 2002 Apr;196(4):241-6.

PubMed [citation]
PMID:
12086152

Details of each submission

From OMIM, SCV000035230.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

This variant, formerly titled CENTRAL HYPOVENTILATION SYNDROME, CONGENITAL, has been reclassified based on its allele frequency in the gnomAD database (v.2.1.1) (Hamosh, 2021).

In a patient with congenital central hypoventilation syndrome (CCHS; 209880), an 8-year-old girl, Kanai et al. (2002) found a 341G-A transition in exon 3 of the RET gene resulting in an arg114-to-his (R114H) amino acid substitution. The mutation was inherited from her healthy father and was absent in 50 healthy Japanese controls. The patient required home ventilation therapy only during sleep and presented normal psychomotor development. She was born at term and showed hypoventilation and/or apnea soon after birth, especially during sleep, and required endotracheal intubation and mechanical ventilation within a few hours after birth. Respiratory function tests performed during sleep showed extremely low or no response to hypercapnia. There was no increase in minute ventilation, even when blood carbon dioxide levels increased, although results of the respiratory function test during the awake state were normal. Screening tests for neuroblastoma were negative and symptoms suggesting Hirschsprung disease (142623) or tumors of neural crest origin were not detected. The patient had very mild constipation (treatment was not needed), strabismus, and incomplete right bundle branch block. Kanai (2002) claimed that this was the first report of a RET gene mutation in a patient with isolated CCHS.

Hamosh (2021) noted that the R114H variant has a frequency of 0.01022 among East Asians (204/19,952) and was identified in one homozygote in gnomAD. This is too high a frequency to account for a severe pediatric disorder.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024