NC_012920.1(MT-CO1):m.6277G>A AND Familial colorectal cancer

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 3, 2009
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:: RCV000010310.3

Allele description [Variation Report for NC_012920.1(MT-CO1):m.6277G>A]

NC_012920.1(MT-CO1):m.6277G>A

Gene:

MT-CO1:mitochondrially encoded cytochrome c oxidase I [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Genomic location:

Preferred name:

NC_012920.1(MT-CO1):m.6277G>A

Other names:

G125D

HGVS:

NC_012920.1:m.6277G>A

Protein change:

GLY125ASP

Links:

OMIM: 516030.0010; dbSNP: rs281865417

NCBI 1000 Genomes Browser:

rs281865417

Condition(s)

Name:: Familial colorectal cancer
Identifiers:: MONDO: MONDO:0023113; MedGen: CN280943

Recent activity

Clear Turn Off Turn On

Vernonia flexuosa internal transcribed spacer 1, partial sequence; 5.8S ribosoma...
Vernonia flexuosa internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|34369929|gb|AY142954.1|

Nucleotide
Daphnia magna isolate NIES, whole genome shotgun sequencing project
Daphnia magna isolate NIES, whole genome shotgun sequencing project
gi|2124572486|gb|JAIFAF000000000.1| F010000000

Nucleotide
ribosomal protein L23 (chloroplast) [Scrophularia ningpoensis]
ribosomal protein L23 (chloroplast) [Scrophularia ningpoensis]
gi|2675821681|gb|WVX52339.1|

Protein

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
SCV000030535	OMIM	no assertion criteria provided	Pathogenic (Mar 3, 2009)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 16407113, 19218458

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000030535

OMIM

no assertion criteria provided

Pathogenic
(Mar 3, 2009)

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

Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.

Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, Leedham SJ, Deheragoda M, Sasieni P, Novelli MR, Jankowski JA, Turnbull DM, Wright NA, McDonald SA.

Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):714-9. Epub 2006 Jan 6.

PubMed [citation]

PMID:: 16407113
PMCID:: PMC1325106

A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.

Namslauer I, Brzezinski P.

Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3402-7. doi: 10.1073/pnas.0811450106. Epub 2009 Feb 13.

PubMed [citation]

PMID:: 19218458
PMCID:: PMC2651238

Details of each submission

From OMIM, SCV000030535.2

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

Description

In colonocytes from cytochrome c oxidase-deficient crypts from a patient with colon cancer (114500), Greaves et al. (2006) identified a 6277A-G transition in the MTCO1 gene, predicted to result in a gly125-to-asp (G125D) substitution at a well-conserved residue.

Namslauer and Brzezinski (2009) used site-directed mutagenesis to alter the residue corresponding to gly125 in the MTCO1 gene of the bacterium Rhodobacter sphaeroides (G171D), and demonstrated that G171D-mutant COX displayed steady-state catalytic activity linked to proton pumping that was approximately 34% of wildtype. In addition, an intrinsic proton leak was found in the enzyme, which would lead to decreased overall energy-conversion efficiency of the respiratory chain, perturbing transport processes such as protein, ion, and metabolite trafficking.

#	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: Jun 9, 2024

ClinVar

Relating variation to medicine