NM_000548.5(TSC2):c.5189C>G (p.Ser1730Cys) AND Tuberous sclerosis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 31, 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:: RCV001232921.8

Allele description [Variation Report for NM_000548.5(TSC2):c.5189C>G (p.Ser1730Cys)]

NM_000548.5(TSC2):c.5189C>G (p.Ser1730Cys)

Gene:

TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.5189C>G (p.Ser1730Cys)

HGVS:

NC_000016.10:g.2088255C>G
NG_005895.1:g.43950C>G
NG_008617.1:g.54966G>C
NM_000548.5:c.5189C>GMANE SELECT
NM_001077183.3:c.4988C>G
NM_001114382.3:c.5120C>G
NM_001318827.2:c.4880C>G
NM_001318829.2:c.4844C>G
NM_001318831.2:c.4457C>G
NM_001318832.2:c.5021C>G
NM_001363528.2:c.4991C>G
NM_001370404.1:c.5057C>G
NM_001370405.1:c.5048C>G
NM_021055.3:c.5060C>G
NP_000539.2:p.Ser1730Cys
NP_001070651.1:p.Ser1663Cys
NP_001107854.1:p.Ser1707Cys
NP_001305756.1:p.Ser1627Cys
NP_001305758.1:p.Ser1615Cys
NP_001305760.1:p.Ser1486Cys
NP_001305761.1:p.Ser1674Cys
NP_001350457.1:p.Ser1664Cys
NP_001357333.1:p.Ser1686Cys
NP_001357334.1:p.Ser1683Cys
NP_066399.2:p.Ser1687Cys
LRG_487t1:c.5189C>G
LRG_487:g.43950C>G
NC_000016.9:g.2138256C>G
NM_000548.3:c.5189C>G

Protein change:

S1486C

Links:

dbSNP: rs2091134565

NCBI 1000 Genomes Browser:

rs2091134565

Molecular consequence:

NM_000548.5:c.5189C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077183.3:c.4988C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001114382.3:c.5120C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318827.2:c.4880C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318829.2:c.4844C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318831.2:c.4457C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318832.2:c.5021C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363528.2:c.4991C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370404.1:c.5057C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370405.1:c.5048C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021055.3:c.5060C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Tuberous sclerosis 2 (TSC2)
Identifiers:: MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

Recent activity

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Homo sapiens OCIA domain containing 2 (OCIAD2), transcript variant 3, mRNA
Homo sapiens OCIA domain containing 2 (OCIAD2), transcript variant 3, mRNA
gi|1890336234|ref|NM_001286773.2|

Nucleotide
Alternaria sp. MY-2011 isolate AM-54 18S small subunit ribosomal RNA gene, parti...
Alternaria sp. MY-2011 isolate AM-54 18S small subunit ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 28S large subunit ribosomal RNA gene, partial sequence
gi|345421921|gb|JN038495.1|

Nucleotide
Alternaria sp. MY-2011 isolate AM-61 18S small subunit ribosomal RNA gene, parti...
Alternaria sp. MY-2011 isolate AM-61 18S small subunit ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 28S large subunit ribosomal RNA gene, partial sequence
gi|345421928|gb|JN038502.1|

Nucleotide
Alternaria sp. MY-2011 isolate AM-62 18S small subunit ribosomal RNA gene, parti...
Alternaria sp. MY-2011 isolate AM-62 18S small subunit ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 28S large subunit ribosomal RNA gene, partial sequence
gi|345421929|gb|JN038503.1|

Nucleotide
solute carrier family 49 member A3 isoform 1 [Homo sapiens]
solute carrier family 49 member A3 isoform 1 [Homo sapiens]
gi|661567306|ref|NP_001281270.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001405494	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 31, 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

SCV001405494

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 31, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001405494.5

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TSC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 1730 of the TSC2 protein (p.Ser1730Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine.

#	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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