NM_001848.2(COL6A1):c.1425del (p.Gly476fs) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 19, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000255364.1

Allele description [Variation Report for NM_001848.2(COL6A1):c.1425del (p.Gly476fs)]

NM_001848.2(COL6A1):c.1425del (p.Gly476fs)

Gene:
COL6A1:collagen type VI alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
21q22.3
Genomic location:
Preferred name:
NM_001848.2(COL6A1):c.1425del (p.Gly476fs)
HGVS:
  • NC_000021.9:g.45997447del
  • NG_008674.1:g.20699del
  • LRG_475t1:c.1425del
  • LRG_475:g.20699del
  • LRG_475p1:p.Gly476fs
  • NC_000021.8:g.47417361del
  • NM_001848.2:c.1425delA
  • p.Gly476Alafs*29
Links:
dbSNP: rs878854398
NCBI 1000 Genomes Browser:
rs878854398
Observations:
2

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000322513GeneDxcriteria provided, single submitter
Likely pathogenic
(Dec 23, 2015)
germlineclinical testing

Citation Link,

SCV000333904EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Jun 19, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown2not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000322513.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.1425delA variant in the COL6A1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1425delA variant causes a frameshift starting with codon Glycine 476, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 29 of the new reading frame, denoted p.Gly476AlafsX29. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1425delA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Protein truncating pathogenic variants downstream of this variant have been reported in the Human Gene Mutation Database in association with COL6A1-related disorders (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants. The c.1425delA variant is a strong candidate for a pathogenic variant, however, the possibility it may be a rare benign variant cannot be excluded.

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

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000333904.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not providednot providednot provided

Last Updated: Sep 29, 2021

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