NC_012920.1(MT-TL1):m.3249G>A AND Kearns-Sayre syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 11, 2010
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000010222.6

Allele description [Variation Report for NC_012920.1(MT-TL1):m.3249G>A]

NC_012920.1(MT-TL1):m.3249G>A

Gene:

MT-TL1:mitochondrially encoded tRNA leucine 1 (UUA/G) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Genomic location:

Preferred name:

NC_012920.1(MT-TL1):m.3249G>A

HGVS:

NC_012920.1:m.3249G>A

Nucleotide change:

3249G-A

Links:

OMIM: 590050.0011; dbSNP: rs199474667

NCBI 1000 Genomes Browser:

rs199474667

Condition(s)

Name:: Kearns-Sayre syndrome
Synonyms:: Ophthalmoplegia, pigmentary degeneration of retina, and cardiomyopathy; Oculocraniosomatic syndrome; Ophthalmoplegia plus syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010787; MedGen: C0022541; Orphanet: 480; OMIM: 530000

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000030446	OMIM	no assertion criteria provided	Uncertain significance (Jun 11, 2010)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 11448301, 20550934

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000030446

OMIM

no assertion criteria provided

Uncertain significance
(Jun 11, 2010)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

A new mitochondrial point mutation in the transfer RNA(Leu) gene in a patient with a clinical phenotype resembling Kearns-Sayre syndrome.

Seneca S, Verhelst H, De Meirleir L, Meire F, Ceuterick-De Groote C, Lissens W, Van Coster R.

Arch Neurol. 2001 Jul;58(7):1113-8. Review.

PubMed [citation]

PMID:: 11448301

Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription.

Yakubovskaya E, Mejia E, Byrnes J, Hambardjieva E, Garcia-Diaz M.

Cell. 2010 Jun 11;141(6):982-93. doi: 10.1016/j.cell.2010.05.018.

PubMed [citation]

PMID:: 20550934
PMCID:: PMC2887341

Details of each submission

From OMIM, SCV000030446.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

This variant, formerly titled KEARNS-SAYRE SYNDROME, has been reclassified as a variant of unknown significance because its pathogenicity has not been confirmed.

Seneca et al. (2001) reported a male patient with clinical signs suggestive of Kearns-Sayre syndrome (530000), including onset at age 22 years of progressive visual failure with retinopathy, external ophthalmoplegia, sensorineural hearing loss, exercise intolerance, muscle weakness, and difficulty swallowing. Skeletal muscle analysis showed decreased activity of complex I and numerous ragged-red fibers. A heteroplasmic 3249G-A point mutation was found in the MTTL1 gene, with a high percentage of mutant mtDNA in skeletal muscle (85%) and in leukocytes (45%). The patient's mother carried less than 5% mutant mtDNA in her blood.

Yakubovskaya et al. (2010) found that 3249G formed a double hydrogen bond with arg387 of MTERF1 (602318). The 3249G-A mutation eliminated this interaction and significantly interfered with transcriptional termination by MTERF1.

#	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		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine