NM_007373.4(SHOC2):c.610A>G (p.Ile204Val) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 19, 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:: RCV000229898.6

Allele description [Variation Report for NM_007373.4(SHOC2):c.610A>G (p.Ile204Val)]

NM_007373.4(SHOC2):c.610A>G (p.Ile204Val)

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.610A>G (p.Ile204Val)

HGVS:

NC_000010.11:g.110964968A>G
NG_028922.1:g.50426A>G
NM_001269039.3:c.610A>G
NM_001324336.2:c.610A>G
NM_001324337.2:c.610A>G
NM_007373.4:c.610A>GMANE SELECT
NP_001255968.1:p.Ile204Val
NP_001311265.1:p.Ile204Val
NP_001311266.1:p.Ile204Val
NP_031399.2:p.Ile204Val
NP_031399.2:p.Ile204Val
LRG_753t1:c.610A>G
LRG_753:g.50426A>G
LRG_753p1:p.Ile204Val
NC_000010.10:g.112724726A>G
NM_007373.3:c.610A>G

Protein change:

I204V

Links:

dbSNP: rs200015085

NCBI 1000 Genomes Browser:

rs200015085

Molecular consequence:

NM_001269039.3:c.610A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324336.2:c.610A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324337.2:c.610A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007373.4:c.610A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000289856	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28074886, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000289856

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 19, 2024)

germline

clinical testing

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

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

Post-mortem whole-exome analysis in a large sudden infant death syndrome cohort with a focus on cardiovascular and metabolic genetic diseases.

Neubauer J, Lecca MR, Russo G, Bartsch C, Medeiros-Domingo A, Berger W, Haas C.

Eur J Hum Genet. 2017 Apr;25(4):404-409. doi: 10.1038/ejhg.2016.199. Epub 2017 Jan 11.

PubMed [citation]

PMID:: 28074886
PMCID:: PMC5386419

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000289856.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 204 of the SHOC2 protein (p.Ile204Val). This variant is present in population databases (rs200015085, gnomAD 0.01%). This missense change has been observed in individual(s) with sudden infant death syndrome (PMID: 28074886). ClinVar contains an entry for this variant (Variation ID: 240838). 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 not expected to disrupt SHOC2 protein function with a negative 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: Sep 29, 2024

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