NM_004369.4(COL6A3):c.3989G>T (p.Ser1330Ile) AND Bethlem myopathy 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 2, 2018
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:: RCV000804588.6

Allele description [Variation Report for NM_004369.4(COL6A3):c.3989G>T (p.Ser1330Ile)]

NM_004369.4(COL6A3):c.3989G>T (p.Ser1330Ile)

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.3989G>T (p.Ser1330Ile)

HGVS:

NC_000002.12:g.237372028C>A
NG_008676.1:g.47180G>T
NM_004369.4:c.3989G>TMANE SELECT
NM_057164.5:c.2768G>T
NM_057165.5:c.3371G>T
NM_057166.5:c.2168G>T
NM_057167.4:c.3371G>T
NP_004360.2:p.Ser1330Ile
NP_004360.2:p.Ser1330Ile
NP_476505.3:p.Ser923Ile
NP_476506.3:p.Ser1124Ile
NP_476507.3:p.Ser723Ile
NP_476508.2:p.Ser1124Ile
LRG_473t1:c.3989G>T
LRG_473:g.47180G>T
LRG_473p1:p.Ser1330Ile
NC_000002.11:g.238280671C>A
NM_004369.3:c.3989G>T

Protein change:

S1124I

Links:

dbSNP: rs779967310

NCBI 1000 Genomes Browser:

rs779967310

Molecular consequence:

NM_004369.4:c.3989G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_057164.5:c.2768G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_057165.5:c.3371G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_057166.5:c.2168G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_057167.4:c.3371G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Bethlem myopathy 1 (BTHLM1A)
Synonyms:: Myopathy, benign congenital, with contractures; BETHLEM MYOPATHY 1A
Identifiers:: MONDO: MONDO:0024530; MedGen: CN029274; Orphanet: 610; OMIM: 158810

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000944505	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 2, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000944505

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 2, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000944505.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL6A3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with isoleucine at codon 1330 of the COL6A3 protein (p.Ser1330Ile). The serine residue is highly conserved and there is a large physicochemical difference between serine and isoleucine.

#	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		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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