NM_004369.4(COL6A3):c.6193G>A (p.Gly2065Ser) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 7, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000050245.9

Allele description

NM_004369.4(COL6A3):c.6193G>A (p.Gly2065Ser)

Gene:

COL6A3:collagen type VI alpha 3 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.3

Genomic location:

Preferred name:

NM_004369.4(COL6A3):c.6193G>A (p.Gly2065Ser)

HGVS:

NC_000002.12:g.237361138C>T
NG_008676.1:g.58070G>A
NM_004369.3:c.6193G>A
NM_004369.4:c.6193G>AMANE SELECT
NM_057166.5:c.4372G>A
NM_057167.3:c.5575G>A
NM_057167.4:c.5575G>A
NP_004360.2:p.Gly2065Ser
NP_004360.2:p.Gly2065Ser
NP_476507.3:p.Gly1458Ser
NP_476508.2:p.Gly1859Ser
NP_476508.2:p.Gly1859Ser
LRG_473t1:c.6193G>A
LRG_473:g.58070G>A
LRG_473p1:p.Gly2065Ser
NC_000002.11:g.238269781C>T
NM_057164.3:c.5692G>A
NM_057165.3:c.5593G>A
NM_057166.3:c.5590G>A
NM_057166.4:c.4372G>A

Protein change:

G1458S

Links:

dbSNP: rs397515332

NCBI 1000 Genomes Browser:

rs397515332

Molecular consequence:

NM_004369.3:c.6193G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004369.4:c.6193G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_057166.5:c.4372G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_057167.3:c.5575G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_057167.4:c.5575G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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
SCV000331198	EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions)	Likely pathogenic (May 3, 2016)	germline	clinical testing	Citation Link,
SCV000620625	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Sep 7, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000331198

EGL Genetic Diagnostics, Eurofins Clinical Diagnostics

criteria provided, single submitter

(EGL Classification Definitions)

Likely pathogenic
(May 3, 2016)

germline

clinical testing

Citation Link,

SCV000620625

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Sep 7, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000331198.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

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

From GeneDx, SCV000620625.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The G2065S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G2065S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs within the Gly-X-Y motif in the triple helical (TH) domain of collagen VI, a region that is well-conserved across species. Additionally, a different missense variant at the same position (G2065D) has been reported in an individual with Ullrich congenital muscular dystrophy (Pace et al., 2008). In silico analysis predicts this variant is probably damaging to the protein structure/function.

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

Last Updated: Nov 20, 2021

ClinVar

Relating variation to medicine