NM_000093.5(COL5A1):c.514G>T (p.Val172Phe) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jul 1, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000199784.12

Allele description [Variation Report for NM_000093.5(COL5A1):c.514G>T (p.Val172Phe)]

NM_000093.5(COL5A1):c.514G>T (p.Val172Phe)

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.514G>T (p.Val172Phe)
Other names:
p.V172F:GTC>TTC
HGVS:
  • NC_000009.12:g.134701193G>T
  • NG_008030.1:g.64388G>T
  • NM_000093.4:c.514G>T
  • NM_000093.5:c.514G>TMANE SELECT
  • NM_001278074.1:c.514G>T
  • NP_000084.3:p.Val172Phe
  • NP_000084.3:p.Val172Phe
  • NP_001265003.1:p.Val172Phe
  • LRG_737t1:c.514G>T
  • LRG_737t2:c.514G>T
  • LRG_737:g.64388G>T
  • LRG_737p1:p.Val172Phe
  • LRG_737p2:p.Val172Phe
  • NC_000009.11:g.137593039G>T
  • NM_000093.3:c.514G>T
Protein change:
V172F
Links:
dbSNP: rs150147262
NCBI 1000 Genomes Browser:
rs150147262
Molecular consequence:
  • NM_000093.4:c.514G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000093.5:c.514G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278074.1:c.514G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
8

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000249872GeneDxcriteria provided, single submitter
Uncertain significance
(Dec 18, 2018)
germlineclinical testing

Citation Link,

SCV001155816CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Likely benign
(Jul 1, 2021)
germlineclinical testing

Citation Link,

SCV001808838Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensusno assertion criteria providedLikely benigngermlineclinical testing

SCV001931512Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedLikely benigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes8not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000249872.14

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

Description

A variant of uncertain significance has been identified in the COL5A1 gene. The V172F variant has not been published as pathogenic or been reported as benign to our knowledge. It has been observed both independently, and in conjunction with other variants, in multiple individuals referred for Marfan/TAAD genetic testing at GeneDx, although segregation data from these individuals is not sufficient to determine the pathogenicity of this variant. This substitution occurs at a position where only amino acids with similar properties to valine (V) are tolerated across species, and V172F is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, V172F does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A1gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). Furthermore, this variant has been observed in 39/65444 (0.06%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).

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

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001155816.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided8not providednot providednot provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808838.1

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001931512.1

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

Last Updated: Oct 30, 2021

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