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NM_001122630.2(CDKN1C):c.578C>T (p.Pro193Leu) AND Beckwith-Wiedemann syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 31, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001053264.7

Allele description

NM_001122630.2(CDKN1C):c.578C>T (p.Pro193Leu)

Gene:
CDKN1C:cyclin dependent kinase inhibitor 1C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_001122630.2(CDKN1C):c.578C>T (p.Pro193Leu)
HGVS:
  • NC_000011.10:g.2884879G>A
  • NG_008022.1:g.5887C>T
  • NM_000076.2:c.611C>T
  • NM_001122630.2:c.578C>TMANE SELECT
  • NM_001122631.2:c.578C>T
  • NM_001362474.2:c.611C>T
  • NM_001362475.2:c.255+323C>T
  • NP_000067.1:p.Pro204Leu
  • NP_001116102.1:p.Pro193Leu
  • NP_001116103.1:p.Pro193Leu
  • NP_001349403.1:p.Pro204Leu
  • LRG_533t1:c.611C>T
  • LRG_533:g.5887C>T
  • LRG_533p1:p.Pro204Leu
  • NC_000011.9:g.2906109G>A
  • NC_000011.9:g.2906109G>A
Protein change:
P193L
Links:
dbSNP: rs2583440
NCBI 1000 Genomes Browser:
rs2583440
Molecular consequence:
  • NM_001362475.2:c.255+323C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000076.2:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001122630.2:c.578C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001122631.2:c.578C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362474.2:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Beckwith-Wiedemann syndrome (BWS)
Synonyms:
Exomphalos macroglossia gigantism syndrome; EMG Syndrome
Identifiers:
MONDO: MONDO:0007534; MedGen: C0004903; Orphanet: 116; OMIM: 130650

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001217520Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 31, 2023) 		germlineclinical testing

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

SCV004212457Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 8, 2023) 		unknownclinical 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
not providedunknownunknownnot 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV001217520.4

#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. 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 CDKN1C protein function. ClinVar contains an entry for this variant (Variation ID: 849327). This variant has not been reported in the literature in individuals affected with CDKN1C-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 204 of the CDKN1C protein (p.Pro204Leu).

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

From Baylor Genetics, SCV004212457.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024