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NM_031407.7(HUWE1):c.12680T>C (p.Leu4227Ser) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 10, 2016
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:
RCV000414013.1

Allele description [Variation Report for NM_031407.7(HUWE1):c.12680T>C (p.Leu4227Ser)]

NM_031407.7(HUWE1):c.12680T>C (p.Leu4227Ser)

Gene:
HUWE1:HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.22
Genomic location:
Preferred name:
NM_031407.7(HUWE1):c.12680T>C (p.Leu4227Ser)
HGVS:
  • NC_000023.11:g.53534667A>G
  • NG_016261.2:g.157067T>C
  • NM_031407.7:c.12680T>CMANE SELECT
  • NP_113584.3:p.Leu4227Ser
  • NC_000023.10:g.53561628A>G
  • NM_031407.4:c.12680T>C
Protein change:
L4227S
Links:
dbSNP: rs1057517893
NCBI 1000 Genomes Browser:
rs1057517893
Molecular consequence:
  • NM_031407.7:c.12680T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000490992GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Oct 10, 2016) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From GeneDx, SCV000490992.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The L4227S variant in the HUWE1 gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The L4227S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L4227S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the HECT domain that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on review of recent literature and internal GeneDx data in the context of the 2015 ACMG standards and guidelines for the interpretation of sequence variants (Richards et al., 2015), we now interpret L4227S as a pathogenic variant,

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

Last Updated: Apr 23, 2022