NM_000071.3(CBS):c.502G>A (p.Val168Met) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: May 19, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000071.3(CBS):c.502G>A (p.Val168Met)]

NM_000071.3(CBS):c.502G>A (p.Val168Met)

CBS:cystathionine beta-synthase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000071.3(CBS):c.502G>A (p.Val168Met)
Other names:
  • NC_000021.9:g.43065645C>T
  • NG_008938.1:g.15286G>A
  • NM_000071.2:c.502G>A
  • NM_000071.3:c.502G>AMANE SELECT
  • NM_001178008.3:c.502G>A
  • NM_001178009.3:c.502G>A
  • NM_001320298.2:c.502G>A
  • NM_001321072.1:c.187G>A
  • NP_000062.1:p.Val168Met
  • NP_000062.1:p.Val168Met
  • NP_001171479.1:p.Val168Met
  • NP_001171480.1:p.Val168Met
  • NP_001307227.1:p.Val168Met
  • NP_001308001.1:p.Val63Met
  • LRG_777t1:c.502G>A
  • LRG_777:g.15286G>A
  • LRG_777p1:p.Val168Met
  • NC_000021.8:g.44485755C>T
  • P35520:p.Val168Met
Protein change:
V168M; VAL168MET
UniProtKB: P35520#VAR_002180; OMIM: 613381.0011; dbSNP: rs121964970
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000071.2:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000071.3:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178008.3:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178009.3:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320298.2:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321072.1:c.187G>A - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000231470EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Aug 29, 2017)
germlineclinical testing

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

Citation Link,

SCV000249683GeneDxcriteria provided, single submitter
Likely pathogenic
(May 19, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing



Surrogate genetics and metabolic profiling for characterization of human disease alleles.

Mayfield JA, Davies MW, Dimster-Denk D, Pleskac N, McCarthy S, Boydston EA, Fink L, Lin XX, Narain AS, Meighan M, Rine J.

Genetics. 2012 Apr;190(4):1309-23. doi: 10.1534/genetics.111.137471. Epub 2012 Jan 20. Erratum in: Genetics. 2012 Oct;192(2):759-60.

PubMed [citation]

A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene.

Kruger WD, Cox DR.

Hum Mol Genet. 1995 Jul;4(7):1155-61.

PubMed [citation]

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000231470.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000249683.15

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


Has been reported in individuals with B6-responsive homocystinuria (Kruger et al., 1995; Shan et al., 1998), as well as an individual with spontaneous coronary artery dissection (SCAD) (Kaadan et al., 2018).; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies in yeast have demonstrated that V168M results in a non-functional allele with impaired CBS function (Shan et al., 1998; Mayfield et al., 2012).; Reported in ClinVar (ClinVar Variant ID# 127; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 10338090, 10531322, 31301157, 8528202, 22267502, 29650765, 9590298, 11230183, 20066033)

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

Last Updated: Oct 25, 2021

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