NM_005633.4(SOS1):c.1648_1650del (p.Leu550del) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 14, 2019
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:: RCV001037790.7

Allele description [Variation Report for NM_005633.4(SOS1):c.1648_1650del (p.Leu550del)]

NM_005633.4(SOS1):c.1648_1650del (p.Leu550del)

Gene:

SOS1:SOS Ras/Rac guanine nucleotide exchange factor 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p22.1

Genomic location:

Preferred name:

NM_005633.4(SOS1):c.1648_1650del (p.Leu550del)

HGVS:

NC_000002.12:g.39022778_39022780del
NG_007530.1:g.102684_102686del
NM_001382394.1:c.1627_1629del
NM_001382395.1:c.1648_1650del
NM_005633.4:c.1648_1650delMANE SELECT
NP_001369323.1:p.Leu543del
NP_001369324.1:p.Leu550del
NP_005624.2:p.Leu550del
NP_005624.2:p.Leu550del
LRG_754t1:c.1648_1650del
LRG_754:g.102684_102686del
LRG_754p1:p.Leu550del
NC_000002.11:g.39249919_39249921del
NM_005633.3:c.1648_1650del

Protein change:

L543del

Links:

dbSNP: rs1669838767

NCBI 1000 Genomes Browser:

rs1669838767

Molecular consequence:

NM_001382394.1:c.1627_1629del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382395.1:c.1648_1650del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_005633.4:c.1648_1650del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001201222	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 14, 2019)	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

SCV001201222

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 14, 2019)

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

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001201222.5

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

Description

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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has been observed in an individual with clinical features of a RASopathy disorder (Invitae). This variant is not present in population databases (ExAC no frequency). This variant, c.1648_1650del, results in the deletion of 1 amino acid(s) of the SOS1 protein (p.Leu550del), but otherwise preserves the integrity of the reading frame.

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine