NM_000503.6(EYA1):c.1748T>C (p.Leu583Pro) AND Rare genetic deafness

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 28, 2012
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:: RCV000041392.5

Allele description [Variation Report for NM_000503.6(EYA1):c.1748T>C (p.Leu583Pro)]

NM_000503.6(EYA1):c.1748T>C (p.Leu583Pro)

Gene:

EYA1:EYA transcriptional coactivator and phosphatase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q13.3

Genomic location:

Preferred name:

NM_000503.6(EYA1):c.1748T>C (p.Leu583Pro)

HGVS:

NC_000008.11:g.71199371A>G
NG_011735.3:g.353760T>C
NM_000503.6:c.1748T>CMANE SELECT
NM_001288574.2:c.1730T>C
NM_001288575.2:c.1382T>C
NM_001370333.1:c.1835T>C
NM_001370334.1:c.1748T>C
NM_001370335.1:c.1748T>C
NM_001370336.1:c.1727T>C
NM_172058.4:c.1748T>C
NM_172059.5:c.1730T>C
NP_000494.2:p.Leu583Pro
NP_001275503.1:p.Leu577Pro
NP_001275504.1:p.Leu461Pro
NP_001357262.1:p.Leu612Pro
NP_001357263.1:p.Leu583Pro
NP_001357264.1:p.Leu583Pro
NP_001357265.1:p.Leu576Pro
NP_742055.1:p.Leu583Pro
NP_742056.2:p.Leu577Pro
NC_000008.10:g.72111606A>G
NG_011735.2:g.167862T>C
NM_000503.4:c.1748T>C
NM_000503.5:c.1748T>C
NM_172058.2:c.1748T>C
Q99502:p.Leu583Pro
c.1748T>C

Protein change:

L461P

Links:

UniProtKB: Q99502#VAR_016869; dbSNP: rs397517920

NCBI 1000 Genomes Browser:

rs397517920

Molecular consequence:

NM_000503.6:c.1748T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001288574.2:c.1730T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001288575.2:c.1382T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370333.1:c.1835T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370334.1:c.1748T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370335.1:c.1748T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370336.1:c.1727T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172058.4:c.1748T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172059.5:c.1730T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

Recent activity

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zinc finger protein 664-like [Periophthalmus magnuspinnatus]
zinc finger protein 664-like [Periophthalmus magnuspinnatus]
gi|2490654147|ref|XP_055082277.1|

Protein
Mus musculus endophilin B1b mRNA, complete cds; alternatively spliced
Mus musculus endophilin B1b mRNA, complete cds; alternatively spliced
gi|18124146|gb|AF272946.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000065086	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Dec 28, 2012)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10991693, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000065086

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Dec 28, 2012)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	3	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Importance of clinical evaluation and molecular testing in the branchio-oto-renal (BOR) syndrome and overlapping phenotypes.

Rickard S, Boxer M, Trompeter R, Bitner-Glindzicz M.

J Med Genet. 2000 Aug;37(8):623-7. No abstract available.

PubMed [citation]

PMID:: 10991693
PMCID:: PMC1734672

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, SCV000065086.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (2)

Description

The Leu583Pro variant in EYA1 has been identified in two probands with clinical features of Branchio-oto-renal syndrome (BOR), was absent from 85 controls, and segregated with clinical features in one affected family member (Rickard 2000, L MM unpublished data). In addition, this residue is conserved across species, and computational analyses (biochemical amino acid properties, homology, PolyPhen2, SIFT) suggest that the variant may impact the protein. In summary, this variant is likely to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		3	not provided	1	not provided

Last Updated: Dec 24, 2023

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