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NM_000214.3(JAG1):c.524G>T (p.Gly175Val) AND Alagille syndrome due to a JAG1 point mutation

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 9, 2021
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:
RCV001365862.8

Allele description [Variation Report for NM_000214.3(JAG1):c.524G>T (p.Gly175Val)]

NM_000214.3(JAG1):c.524G>T (p.Gly175Val)

Gene:
JAG1:jagged canonical Notch ligand 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20p12.2
Genomic location:
Preferred name:
NM_000214.3(JAG1):c.524G>T (p.Gly175Val)
HGVS:
  • NC_000020.11:g.10658638C>A
  • NG_007496.1:g.20409G>T
  • NM_000214.3:c.524G>TMANE SELECT
  • NP_000205.1:p.Gly175Val
  • LRG_1191t1:c.524G>T
  • LRG_1191:g.20409G>T
  • LRG_1191p1:p.Gly175Val
  • NC_000020.10:g.10639286C>A
  • NM_000214.2:c.524G>T
Protein change:
G175V
Links:
dbSNP: rs2122623743
NCBI 1000 Genomes Browser:
rs2122623743
Molecular consequence:
  • NM_000214.3:c.524G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Alagille syndrome due to a JAG1 point mutation
Synonyms:
HEPATIC DUCTULAR HYPOPLASIA, SYNDROMATIC; Alagille syndrome 1; JAG1-Related Alagille Syndrome
Identifiers:
MONDO: MONDO:0016862; MedGen: C1956125; Orphanet: 52; OMIM: 118450

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001562147Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 9, 2021) 		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, SCV001562147.5

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with JAG1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 175 of the JAG1 protein (p.Gly175Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine.

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

Last Updated: Sep 29, 2024