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NM_004369.4(COL6A3):c.8861C>A (p.Pro2954His) AND Bethlem myopathy 1A

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 26, 2022
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:
RCV003114854.12

Allele description [Variation Report for NM_004369.4(COL6A3):c.8861C>A (p.Pro2954His)]

NM_004369.4(COL6A3):c.8861C>A (p.Pro2954His)

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.8861C>A (p.Pro2954His)
HGVS:
  • NC_000002.12:g.237336239G>T
  • NG_008676.1:g.82969C>A
  • NG_098092.1:g.557G>T
  • NG_098093.1:g.56G>T
  • NM_004369.4:c.8861C>AMANE SELECT
  • NM_057164.3:c.8360C>A
  • NM_057165.3:c.8261C>A
  • NM_057166.5:c.7040C>A
  • NM_057167.4:c.8243C>A
  • NP_004360.2:p.Pro2954His
  • NP_004360.2:p.Pro2954His
  • NP_476505.2:p.Pro2787His
  • NP_476506.2:p.Pro2754His
  • NP_476507.3:p.Pro2347His
  • NP_476508.2:p.Pro2748His
  • LRG_473t1:c.8861C>A
  • LRG_473:g.82969C>A
  • LRG_473p1:p.Pro2954His
  • NC_000002.11:g.238244882G>T
  • NM_004369.3:c.8861C>A
Protein change:
P2347H
Molecular consequence:
  • NM_004369.4:c.8861C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057164.3:c.8360C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057165.3:c.8261C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057166.5:c.7040C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057167.4:c.8243C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Bethlem myopathy 1A
Synonyms:
Myopathy, benign congenital, with contractures; Bethlem myopathy 1
Identifiers:
MONDO: MONDO:0024530; MedGen: CN029274; Orphanet: 610; OMIM: 158810

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003785317Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 26, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003785317.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL6A3 protein function. This variant has not been reported in the literature in individuals affected with COL6A3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 2954 of the COL6A3 protein (p.Pro2954His).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024