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NM_000093.5(COL5A1):c.4121C>T (p.Thr1374Met) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
May 13, 2024
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:
RCV004689755.1

Allele description [Variation Report for NM_000093.5(COL5A1):c.4121C>T (p.Thr1374Met)]

NM_000093.5(COL5A1):c.4121C>T (p.Thr1374Met)

Gene:
COL5A1:collagen type V alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.3
Genomic location:
Preferred name:
NM_000093.5(COL5A1):c.4121C>T (p.Thr1374Met)
HGVS:
  • NC_000009.12:g.134815987C>T
  • NG_008030.1:g.179182C>T
  • NM_000093.5:c.4121C>TMANE SELECT
  • NM_001278074.1:c.4121C>T
  • NP_000084.3:p.Thr1374Met
  • NP_000084.3:p.Thr1374Met
  • NP_001265003.1:p.Thr1374Met
  • LRG_737t1:c.4121C>T
  • LRG_737t2:c.4121C>T
  • LRG_737:g.179182C>T
  • LRG_737p1:p.Thr1374Met
  • LRG_737p2:p.Thr1374Met
  • NC_000009.11:g.137707833C>T
  • NM_000093.3:c.4121C>T
  • NM_000093.4:c.4121C>T
Protein change:
T1374M
Links:
dbSNP: rs151115748
NCBI 1000 Genomes Browser:
rs151115748
Molecular consequence:
  • NM_000093.5:c.4121C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278074.1:c.4121C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV005184780Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely benign
(May 13, 2024)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

High Prevalence of Collagenopathies in Preterm- and Term-Born Children With Periventricular Venous Hemorrhagic Infarction.

Ilves N, Pajusalu S, Kahre T, Laugesaar R, Ĺ amarina U, Loorits D, Kool P, Ilves P.

J Child Neurol. 2023 May;38(6-7):373-388. doi: 10.1177/08830738231186233. Epub 2023 Jul 10.

PubMed [citation]
PMID:
37427422
PMCID:
PMC10467006

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005184780.1

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

Description

Variant summary: COL5A1 c.4121C>T (p.Thr1374Met) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. In addition, this variant disrupts the penultimate nucleotide of exon 52, and therefore can affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00023 in 251418 control chromosomes. The observed variant frequency is approximately 7.25 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL5A1 causing Ehlers-Danlos Syndrome phenotype (3.1e-05), strongly suggesting that the variant is benign. c.4121C>T has been reported in the literature as a variant of uncertain significance in at least one individual with a diagnosis or suspicion of Ehlers-Danlos Syndrome (e.g., Ilves_2023), however without strong evidence for causality (e.g., lack of co-segregation data). These report(s) do not provide unequivocal conclusions about association of the variant with Ehlers-Danlos Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 37427422). ClinVar contains an entry for this variant (Variation ID: 419573). Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Nov 10, 2024