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NM_004369.4(COL6A3):c.985G>A (p.Val329Met) AND Bethlem myopathy 1A

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 3, 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:
RCV001007810.5

Allele description [Variation Report for NM_004369.4(COL6A3):c.985G>A (p.Val329Met)]

NM_004369.4(COL6A3):c.985G>A (p.Val329Met)

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.985G>A (p.Val329Met)
HGVS:
  • NC_000002.12:g.237387909C>T
  • NG_008676.1:g.31299G>A
  • NM_004369.4:c.985G>AMANE SELECT
  • NM_057164.5:c.92-6410G>A
  • NM_057165.5:c.367G>A
  • NM_057166.5:c.92-6410G>A
  • NM_057167.4:c.367G>A
  • NP_004360.2:p.Val329Met
  • NP_476506.3:p.Val123Met
  • NP_476508.2:p.Val123Met
  • NP_476508.2:p.Val123Met
  • LRG_473:g.31299G>A
  • NC_000002.11:g.238296552C>T
  • NC_000002.11:g.238296552C>T
  • NM_057167.3:c.367G>A
Protein change:
V123M
Links:
dbSNP: rs542283928
NCBI 1000 Genomes Browser:
rs542283928
Molecular consequence:
  • NM_057164.5:c.92-6410G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_057166.5:c.92-6410G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_004369.4:c.985G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057165.5:c.367G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057167.4:c.367G>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

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001167501Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
no assertion criteria provided
Uncertain significanceinheritedresearch

SCV003786419Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 3, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedinheritedyes41not providednot providedyesresearch

Citations

PubMed

The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.

Pehlivan D, Bayram Y, Gunes N, Coban Akdemir Z, Shukla A, Bierhals T, Tabakci B, Sahin Y, Gezdirici A, Fatih JM, Gulec EY, Yesil G, Punetha J, Ocak Z, Grochowski CM, Karaca E, Albayrak HM, Radhakrishnan P, Erdem HB, Sahin I, Yildirim T, Bayhan IA, et al.

Am J Hum Genet. 2019 Jul 3;105(1):132-150. doi: 10.1016/j.ajhg.2019.05.015. Epub 2019 Jun 20.

PubMed [citation]
PMID:
31230720
PMCID:
PMC6612529

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV001167501.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providedyesresearchnot provided

Description

Two genes were thought to be involved in this family's phenotype including autosomal dominant FBN2 c.4094G>C and autosomal recessive COL6A3 c.367G>A variant

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided4not provided1not provided

From Invitae, SCV003786419.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

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. ClinVar contains an entry for this variant (Variation ID: 689566). This missense change has been observed in individual(s) with COL6A3-related conditions (PMID: 31230720). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 329 of the COL6A3 protein (p.Val329Met).

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

Last Updated: Apr 15, 2024