NM_005343.4(HRAS):c.37G>T (p.Gly13Cys) AND RASopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 24, 2018
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:: RCV000149831.4

Allele description [Variation Report for NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)]

NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)

Genes:

HRAS:HRas proto-oncogene, GTPase [Gene - OMIM - HGNC]
LRRC56:leucine rich repeat containing 56 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)

Other names:

p.G13C:GGT>TGT; NM_005343.3(HRAS):c.37G>T

HGVS:

NC_000011.10:g.534286C>A
NG_007666.1:g.6265G>T
NM_001130442.3:c.37G>T
NM_001318054.2:c.-283G>T
NM_005343.4:c.37G>TMANE SELECT
NM_176795.5:c.37G>T
NP_001123914.1:p.Gly13Cys
NP_005334.1:p.Gly13Cys
NP_789765.1:p.Gly13Cys
LRG_506t1:c.37G>T
LRG_506:g.6265G>T
LRG_506p1:p.Gly13Cys
NC_000011.9:g.534286C>A
NM_005343.2:c.37G>T
NM_005343.3:c.37G>T
P01112:p.Gly13Cys
c.37G>T

Protein change:

G13C; GLY13CYS

Links:

UniProtKB: P01112#VAR_026107; OMIM: 190020.0007; dbSNP: rs104894228

NCBI 1000 Genomes Browser:

rs104894228

Molecular consequence:

NM_001318054.2:c.-283G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001130442.3:c.37G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005343.4:c.37G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_176795.5:c.37G>T - 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
SCV000196675	Baylor Genetics	no assertion criteria provided	Pathogenic	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21495179, 21438134
SCV000917529	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 24, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21438134, 23429430 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000196675

Baylor Genetics

no assertion criteria provided

Pathogenic

unknown

clinical testing

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

SCV000917529

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 24, 2018)

germline

clinical testing

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

Citation Link

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
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Neurocognitive, adaptive, and behavioral functioning of individuals with Costello syndrome: a review.

Axelrad ME, Schwartz DD, Katzenstein JM, Hopkins E, Gripp KW.

Am J Med Genet C Semin Med Genet. 2011 May 15;157C(2):115-22. doi: 10.1002/ajmg.c.30299. Epub 2011 Apr 14. Review.

PubMed [citation]

PMID:: 21495179

Phenotypic analysis of individuals with Costello syndrome due to HRAS p.G13C.

Gripp KW, Hopkins E, Sol-Church K, Stabley DL, Axelrad ME, Doyle D, Dobyns WB, Hudson C, Johnson J, Tenconi R, Graham GE, Sousa AB, Heller R, Piccione M, Corsello G, Herman GE, Tartaglia M, Lin AE.

Am J Med Genet A. 2011 Apr;155A(4):706-16. doi: 10.1002/ajmg.a.33884. Epub 2011 Mar 15.

PubMed [citation]

PMID:: 21438134
PMCID:: PMC4166651

See all PubMed Citations (3)

Details of each submission

From Baylor Genetics, SCV000196675.1

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

Description

Variant classified using ACMG guidelines

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917529.1

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

Description

Variant summary: HRAS c.37G>T (p.Gly13Cys) results in a non-conservative amino acid change located in the Small GTP-binding protein domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 276492 control chromosomes (gnomAD). c.37G>T has been reported in the literature in multiple individuals affected with Noonan Syndrome and Related Conditions and occurs at a codon that is known to be associated with disease (McCormick_2013, Gripp_2011). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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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