NM_000203.5(IDUA):c.1163C>A (p.Thr388Lys) AND Mucopolysaccharidosis type 1

Clinical significance:Likely pathogenic (Last evaluated: Jan 13, 2020)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001249042.1

Allele description [Variation Report for NM_000203.5(IDUA):c.1163C>A (p.Thr388Lys)]

NM_000203.5(IDUA):c.1163C>A (p.Thr388Lys)

Gene:
IDUA:alpha-L-iduronidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p16.3
Genomic location:
Preferred name:
NM_000203.5(IDUA):c.1163C>A (p.Thr388Lys)
HGVS:
  • NC_000004.12:g.1002459C>A
  • NG_008103.1:g.20463C>A
  • NM_000203.5:c.1163C>AMANE SELECT
  • NM_001363576.1:c.767C>A
  • NP_000194.2:p.Thr388Lys
  • NP_001350505.1:p.Thr256Lys
  • LRG_1277t1:c.1163C>A
  • LRG_1277:g.20463C>A
  • LRG_1277p1:p.Thr388Lys
  • NC_000004.11:g.996247C>A
  • NM_000203.3:c.1163C>A
  • NM_000203.4(IDUA):c.1163C>A
  • NR_110313.1:n.1251C>A
  • p.Thr388Lys
Protein change:
T256K
Links:
dbSNP: rs794727896
NCBI 1000 Genomes Browser:
rs794727896
Molecular consequence:
  • NM_000203.5:c.1163C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363576.1:c.767C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_110313.1:n.1251C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Mucopolysaccharidosis type 1 (MPS1)
Synonyms:
Mucopolysaccharidosis type I; MPS 1; Attenuated MPS I (subtype); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0001586; MedGen: C0023786

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001422980Broad Institute Rare Disease Group, Broad Instituteno assertion criteria providedLikely pathogenic
(Jan 13, 2020)
germlinecuration

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Report of 5 novel mutations of the α-L-iduronidase gene and comparison of Korean mutations in relation with those of Japan or China in patients with mucopolysaccharidosis I.

Kwak MJ, Huh R, Kim J, Park HD, Cho SY, Jin DK.

BMC Med Genet. 2016 Aug 12;17(1):58. doi: 10.1186/s12881-016-0319-x.

PubMed [citation]
PMID:
27520059
PMCID:
PMC4983032

Details of each submission

From Broad Institute Rare Disease Group, Broad Institute, SCV001422980.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The p.Thr388Lys variant in IDUA has been reported in 1 individual with mucopolysaccharidosis (MPS) (PMID: 27520059) and has been identified in 0.009% (1/10974) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs794727896). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (VariationID: 198686) as a VUS by Counsyl and as likely pathogenic by EGL Genetic Diagnostics. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. One additional pathogenic variant, resulting in a different amino acid change at the same position, p.Thr388Arg, has been reported in association with disease in the literature and ClinVar, supporting that a change at this position may not be tolerated (PMID: 28752568, 21963080, 28728811; Variation ID: 496834). The presence of this variant in 1 affected homozygote with MPS increases the likelihood that the p.Thr388Lys variant is pathogenic (PMID: 27520059). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PM5, PP3, PM3_supporting (Richards 2015).

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

Last Updated: Oct 7, 2021

Support Center