NM_001330723.2(SNX27):c.1025A>G (p.Tyr342Cys) AND Severe myoclonic epilepsy in infancy

Clinical significance:Uncertain significance (Last evaluated: Feb 18, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001060080.1

Allele description [Variation Report for NM_001330723.2(SNX27):c.1025A>G (p.Tyr342Cys)]

NM_001330723.2(SNX27):c.1025A>G (p.Tyr342Cys)

Gene:
SNX27:sorting nexin 27 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q21.3
Genomic location:
Preferred name:
NM_001330723.2(SNX27):c.1025A>G (p.Tyr342Cys)
HGVS:
  • NC_000001.11:g.151668511A>G
  • NM_001330723.2:c.1025A>GMANE SELECT
  • NM_030918.6:c.1025A>G
  • NP_001317652.1:p.Tyr342Cys
  • NP_112180.4:p.Tyr342Cys
  • NC_000001.10:g.151640987A>G
  • NM_030918.5:c.1025A>G
Protein change:
Y342C
Molecular consequence:
  • NM_001330723.2:c.1025A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_030918.6:c.1025A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Severe myoclonic epilepsy in infancy (DRVT)
Synonyms:
Epilepsy, Myoclonic, Infantile, Severe; Dravet syndrome; Epileptic encephalopathy, early infantile, 6 (Dravet syndrome)
Identifiers:
MONDO: MONDO:0100135; MedGen: C0751122; Orphanet: 33069; OMIM: 607208

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001224742Invitaecriteria provided, single submitter
Uncertain significance
(Feb 18, 2019)
germlineclinical testing

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

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

Details of each submission

From Invitae, SCV001224742.2

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

Description

This sequence change replaces tyrosine with cysteine at codon 342 of the SNX27 protein (p.Tyr342Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SNX27-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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