NM_000071.3(CBS):c.215A>T (p.Lys72Ile) AND Classic homocystinuria

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Nov 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV001086812.4

Allele description [Variation Report for NM_000071.3(CBS):c.215A>T (p.Lys72Ile)]

NM_000071.3(CBS):c.215A>T (p.Lys72Ile)

Gene:
CBS:cystathionine beta-synthase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.3
Genomic location:
Preferred name:
NM_000071.3(CBS):c.215A>T (p.Lys72Ile)
Other names:
p.K72I:AAA>ATA
HGVS:
  • NC_000021.9:g.43068610T>A
  • NG_008938.1:g.12321A>T
  • NM_000071.2:c.215A>T
  • NM_000071.3:c.215A>TMANE SELECT
  • NM_001178008.3:c.215A>T
  • NM_001178009.3:c.215A>T
  • NM_001320298.2:c.215A>T
  • NP_000062.1:p.Lys72Ile
  • NP_000062.1:p.Lys72Ile
  • NP_001171479.1:p.Lys72Ile
  • NP_001171480.1:p.Lys72Ile
  • NP_001307227.1:p.Lys72Ile
  • LRG_777t1:c.215A>T
  • LRG_777:g.12321A>T
  • LRG_777p1:p.Lys72Ile
  • NC_000021.8:g.44488720T>A
Protein change:
K72I
Links:
dbSNP: rs192232907
NCBI 1000 Genomes Browser:
rs192232907
Molecular consequence:
  • NM_000071.2:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000071.3:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178008.3:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178009.3:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320298.2:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Classic homocystinuria
Synonyms:
HOMOCYSTINURIA WITH OR WITHOUT RESPONSE TO PYRIDOXINE; Homocystinuria due to CBS deficiency; Homocystinuria due to cystathionine beta-synthase deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009352; MedGen: C0751202; Orphanet: 394; OMIM: 236200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000649830Invitaecriteria provided, single submitter
Likely benign
(Nov 21, 2020)
germlineclinical testing

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

SCV001298525Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

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

Citation Link,

SCV001455979Natera, Inc.no assertion criteria providedLikely benign
(May 30, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Cross-talk between the catalytic core and the regulatory domain in cystathionine β-synthase: study by differential covalent labeling and computational modeling.

Hnízda A, Spiwok V, Jurga V, Kozich V, Kodícek M, Kraus JP.

Biochemistry. 2010 Dec 14;49(49):10526-34. doi: 10.1021/bi101384m. Epub 2010 Nov 17.

PubMed [citation]
PMID:
21062078
PMCID:
PMC3146298

Details of each submission

From Invitae, SCV000649830.4

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

From Illumina Clinical Services Laboratory,Illumina, SCV001298525.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From Natera, Inc., SCV001455979.1

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

Last Updated: Nov 10, 2021

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