U.S. flag

An official website of the United States government

NM_000161.3(GCH1):c.145C>T (p.Pro49Ser) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 16, 2023
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:
RCV003783778.2

Allele description [Variation Report for NM_000161.3(GCH1):c.145C>T (p.Pro49Ser)]

NM_000161.3(GCH1):c.145C>T (p.Pro49Ser)

Gene:
GCH1:GTP cyclohydrolase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q22.2
Genomic location:
Preferred name:
NM_000161.3(GCH1):c.145C>T (p.Pro49Ser)
HGVS:
  • NC_000014.9:g.54902519G>A
  • NG_008647.1:g.5306C>T
  • NG_008647.2:g.5307C>T
  • NG_190113.1:g.79G>A
  • NM_000161.3:c.145C>TMANE SELECT
  • NM_001024024.2:c.145C>T
  • NM_001024070.2:c.145C>T
  • NM_001024071.2:c.145C>T
  • NM_001424104.1:c.145C>T
  • NP_000152.1:p.Pro49Ser
  • NP_001019195.1:p.Pro49Ser
  • NP_001019241.1:p.Pro49Ser
  • NP_001019242.1:p.Pro49Ser
  • NP_001411033.1:p.Pro49Ser
  • NC_000014.8:g.55369237G>A
Protein change:
P49S
Molecular consequence:
  • NM_000161.3:c.145C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024024.2:c.145C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024070.2:c.145C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024071.2:c.145C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001424104.1:c.145C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dystonia 5 (DRD)
Synonyms:
Dystonia, progressive, with diurnal variation; Dystonia-Parkinsonism with diurnal fluctuation; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007495; MedGen: C1851920; Orphanet: 98808; OMIM: 128230
Name:
GTP cyclohydrolase I deficiency
Identifiers:
MONDO: MONDO:0100184; MedGen: C0268467

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004571542Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 16, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004571542.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 49 of the GCH1 protein (p.Pro49Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GCH1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GCH1 protein function. 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.

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

Last Updated: Sep 29, 2024