NM_007373.4(SHOC2):c.1555C>G (p.Leu519Val) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 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:: RCV002006028.3

Allele description [Variation Report for NM_007373.4(SHOC2):c.1555C>G (p.Leu519Val)]

NM_007373.4(SHOC2):c.1555C>G (p.Leu519Val)

Gene:

SHOC2:SHOC2 leucine rich repeat scaffold protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q25.2

Genomic location:

Preferred name:

NM_007373.4(SHOC2):c.1555C>G (p.Leu519Val)

HGVS:

NC_000010.11:g.111011624C>G
NG_028922.1:g.97082C>G
NM_001269039.3:c.1417C>G
NM_001324336.2:c.1555C>G
NM_001324337.2:c.1555C>G
NM_007373.4:c.1555C>GMANE SELECT
NP_001255968.1:p.Leu473Val
NP_001311265.1:p.Leu519Val
NP_001311266.1:p.Leu519Val
NP_031399.2:p.Leu519Val
LRG_753:g.97082C>G
NC_000010.10:g.112771382C>G
NR_136749.2:n.906C>G

Protein change:

L473V

Links:

dbSNP: rs2134182984

NCBI 1000 Genomes Browser:

rs2134182984

Molecular consequence:

NM_001269039.3:c.1417C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324336.2:c.1555C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324337.2:c.1555C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007373.4:c.1555C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136749.2:n.906C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

Recent activity

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BioAssays, RNAi Target, Active for Gene (Select 286) (1)
PubChem BioAssay
532732_1
532732_1

GEO DataSets
GEO DataSets Links for BioSample (Select 7411093) (1)
GEO DataSets
Taxonomy Links for Nucleotide (Select 2217397325) (1)
Taxonomy
Vibrio sp. 10N.286.45.B6, whole genome shotgun sequencing project
Vibrio sp. 10N.286.45.B6, whole genome shotgun sequencing project
gi|1326757861|gb|MCWK00000000.1|MCW 0000

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002274027	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 11, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002274027

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 11, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV002274027.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 519 of the SHOC2 protein (p.Leu519Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SHOC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1484743). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SHOC2 protein function with a positive predictive value of 80%. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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