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NM_022124.6(CDH23):c.752C>T (p.Pro251Leu) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 12, 2015
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:
RCV000223293.4

Allele description [Variation Report for NM_022124.6(CDH23):c.752C>T (p.Pro251Leu)]

NM_022124.6(CDH23):c.752C>T (p.Pro251Leu)

Gene:
CDH23:cadherin related 23 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.1
Genomic location:
Preferred name:
NM_022124.6(CDH23):c.752C>T (p.Pro251Leu)
HGVS:
  • NC_000010.11:g.71570917C>T
  • NG_008835.1:g.178971C>T
  • NM_001171930.2:c.752C>T
  • NM_001171931.2:c.752C>T
  • NM_001171932.2:c.752C>T
  • NM_022124.6:c.752C>TMANE SELECT
  • NM_052836.4:c.752C>T
  • NP_001165401.1:p.Pro251Leu
  • NP_001165402.1:p.Pro251Leu
  • NP_001165403.1:p.Pro251Leu
  • NP_071407.4:p.Pro251Leu
  • NP_443068.1:p.Pro251Leu
  • NC_000010.10:g.73330674C>T
  • NM_022124.5:c.752C>T
Protein change:
P251L
Links:
dbSNP: rs746961144
NCBI 1000 Genomes Browser:
rs746961144
Molecular consequence:
  • NM_001171930.2:c.752C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171931.2:c.752C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171932.2:c.752C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022124.6:c.752C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_052836.4:c.752C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000271569Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(May 12, 2015) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271569.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Pro251Leu var iant in CDH23 has not been previously reported in individuals with hearing loss, but has been identified in 1/9806 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). The proline (Pro) at position 251 is not evolutionarily conserved across species, with 2 mammals (dolphin and killer whale) and 10 fish species having a leucine (Leu) at this position. Addi tional computational prediction tools do not provide strong support for or again st an impact to the protein. This variant is located in the last three bases of the exon, which is part of the 5? splice region. Computational tools do not sugg est an impact to splicing; however, this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Pr o251Leu variant is uncertain, the lack of evolutionarily conservation suggests t hat it is more likely to be benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Sep 29, 2024