COL6A3 D2831H - GET-Evidence

Curation:
Currentness:

COL6A3 D2831H

(COL6A3 Asp2831His)


Short summary

Probably benign, reported by Pan et al. as a presumed-nonpathogenic variant in the gene.

Variant evidence
Computational 1

No polyphen information, BLOSUM100 score indicates Asp to His is not very disruptive.

Functional -
Case/Control 3

Allele frequency supports no severe pathogenic effect

Familial 1

Pan et al. report the variant was found in both affected and unaffected family members.

See Pan TC et al. 1998 (9536084).

 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Likely benign

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr2:238247734: 6.8% (730/10758) in EVS
  • G @ chr2:237912472: 4.7% (6/128) in GET-Evidence
  • Frequency shown in summary reports: 6.8% (730/10758)

Publications
 

Pan TC, Zhang RZ, Pericak-Vance MA, Tandan R, Fries T, Stajich JM, Viles K, Vance JM, Chu ML, Speer MC. Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy. Hum Mol Genet. 1998 May;7(5):807-12. PubMed PMID: 9536084.

This variant is reported as a presumed-nonpathogenic sequence variation found in both affected and unaffected family members (Table 2, position 8746 in EMBL X52022).

Baker NL, Mörgelin M, Peat R, Goemans N, North KN, Bateman JF, Lamandé SR. Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy. Hum Mol Genet. 2005 Jan 15;14(2):279-93. Epub 2004 Nov 24. PubMed PMID: 15563506.

This variant is reported to be heterozygous in patient UCMD3, refencing Pan et al. Other variants are reported as well, it is unclear which variant the authors consider to be causal.

This patient’s cell line actually had collagen VI appear normal in most tests performed. However, the authors report unusual large aggregates and hypothesize that there is some structural abnormality in collagen VI in this patient even though no other biosynthetic or assembly abnormalities were found.

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het G @ chr2:238247734

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het G @ chr2:238247734

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het G @ chr2:238247734

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het G @ chr2:238247734

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het G @ chr2:238247734

 

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het G @ chr2:238247734

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het G @ chr2:238247734

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het G @ chr2:238247734

 

GS06994 - var-GS06994-1100-36-ASM
het G @ chr2:237912473

 

GS10851 - var-GS10851-1100-36-ASM
het G @ chr2:237912473

 

GS12004 - var-GS12004-1100-36-ASM
het G @ chr2:237912473

 

Other external references
 

    dbSNP
  • rs36104025
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in