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NM_022124.6(CDH23):c.1672G>A (p.Val558Met) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 31, 2017
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:
RCV000220115.5

Allele description [Variation Report for NM_022124.6(CDH23):c.1672G>A (p.Val558Met)]

NM_022124.6(CDH23):c.1672G>A (p.Val558Met)

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.1672G>A (p.Val558Met)
HGVS:
  • NC_000010.11:g.71677613G>A
  • NG_008835.1:g.285667G>A
  • NM_001171930.2:c.1672G>A
  • NM_001171931.2:c.1672G>A
  • NM_022124.6:c.1672G>AMANE SELECT
  • NP_001165401.1:p.Val558Met
  • NP_001165402.1:p.Val558Met
  • NP_071407.4:p.Val558Met
  • NC_000010.10:g.73437370G>A
  • NM_022124.5:c.1672G>A
Protein change:
V558M
Links:
dbSNP: rs780661396
NCBI 1000 Genomes Browser:
rs780661396
Molecular consequence:
  • NM_001171930.2:c.1672G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171931.2:c.1672G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022124.6:c.1672G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

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
SCV000271551Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Mar 31, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not 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, SCV000271551.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Val558Met var iant in CDH23 has been previously identified by our laboratory in one individual with hearing loss due to an alternate etiology. This variant has been identifie d in 8/35828 European and 4/10394 South Asian chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs780661396). Althoug h this variant has been seen in the general population, its frequency is not hig h enough to rule out a pathogenic role. The valine (Val) at position 558 is not conserved in mammals or evolutionarily distant species and 2 mammals (chimpanze e and elephant) carry a methionine (Met), supporting that this change may be tol erated. Additional computational prediction tools suggest that the p.Val558Met variant may not impact the protein, though this information is not predictive en ough to rule out pathogenicity. In summary, while the clinical significance of t he p.Val558Met variant is uncertain, the conservation and computational data sug gest that it is more likely to be benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

Last Updated: May 1, 2024