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NM_000435.3(NOTCH3):c.1715C>T (p.Pro572Leu) AND not provided

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 17, 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:
RCV003560091.2

Allele description [Variation Report for NM_000435.3(NOTCH3):c.1715C>T (p.Pro572Leu)]

NM_000435.3(NOTCH3):c.1715C>T (p.Pro572Leu)

Gene:
NOTCH3:notch receptor 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.12
Genomic location:
Preferred name:
NM_000435.3(NOTCH3):c.1715C>T (p.Pro572Leu)
HGVS:
  • NC_000019.10:g.15187230G>A
  • NG_009819.1:g.18752C>T
  • NM_000435.3:c.1715C>TMANE SELECT
  • NP_000426.2:p.Pro572Leu
  • NC_000019.9:g.15298041G>A
Protein change:
P572L
Molecular consequence:
  • NM_000435.3:c.1715C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004297932Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 17, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

NOTCH3 variants in patients with subcortical vascular cognitive impairment: a comparison with typical CADASIL patients.

Yoon CW, Kim YE, Seo SW, Ki CS, Choi SH, Kim JW, Na DL.

Neurobiol Aging. 2015 Aug;36(8):2443.e1-7. doi: 10.1016/j.neurobiolaging.2015.04.009. Epub 2015 Apr 25.

PubMed [citation]
PMID:
26002683

Clinical and imaging features of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cysteine-sparing NOTCH3 mutations.

Kim H, Lim YM, Lee EJ, Oh YJ, Kim KK.

PLoS One. 2020;15(6):e0234797. doi: 10.1371/journal.pone.0234797.

PubMed [citation]
PMID:
32555735
PMCID:
PMC7302479
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297932.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 572 of the NOTCH3 protein (p.Pro572Leu). This variant is present in population databases (rs773507679, gnomAD 0.03%). This missense change has been observed in individual(s) with NOTCH3-related conditions (PMID: 26002683, 32555735, 34720994). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NOTCH3 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