NM_000368.5(TSC1):c.679G>A (p.Val227Met) AND Tuberous sclerosis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 13, 2022
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:: RCV003049791.3

Allele description [Variation Report for NM_000368.5(TSC1):c.679G>A (p.Val227Met)]

NM_000368.5(TSC1):c.679G>A (p.Val227Met)

Gene:

TSC1:TSC complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_000368.5(TSC1):c.679G>A (p.Val227Met)

HGVS:

NC_000009.12:g.132921421C>T
NG_012386.1:g.28213G>A
NM_000368.5:c.679G>AMANE SELECT
NM_001162426.2:c.679G>A
NM_001162427.2:c.526G>A
NM_001362177.2:c.316G>A
NM_001406592.1:c.679G>A
NM_001406593.1:c.679G>A
NM_001406594.1:c.679G>A
NM_001406595.1:c.679G>A
NM_001406596.1:c.679G>A
NM_001406597.1:c.679G>A
NM_001406598.1:c.679G>A
NM_001406599.1:c.679G>A
NM_001406600.1:c.679G>A
NM_001406601.1:c.679G>A
NM_001406602.1:c.679G>A
NM_001406603.1:c.679G>A
NM_001406604.1:c.679G>A
NM_001406605.1:c.679G>A
NM_001406606.1:c.679G>A
NM_001406607.1:c.679G>A
NM_001406608.1:c.679G>A
NM_001406609.1:c.679G>A
NM_001406610.1:c.526G>A
NM_001406611.1:c.526G>A
NM_001406612.1:c.526G>A
NM_001406613.1:c.526G>A
NM_001406614.1:c.316G>A
NM_001406615.1:c.316G>A
NM_001406616.1:c.316G>A
NM_001406617.1:c.316G>A
NM_001406618.1:c.316G>A
NM_001406619.1:c.316G>A
NM_001406620.1:c.316G>A
NM_001406621.1:c.316G>A
NM_001406622.1:c.316G>A
NM_001406623.1:c.316G>A
NM_001406624.1:c.316G>A
NM_001406625.1:c.316G>A
NM_001406630.1:c.-415G>A
NP_000359.1:p.Val227Met
NP_000359.1:p.Val227Met
NP_000359.1:p.Val227Met
NP_001155898.1:p.Val227Met
NP_001155899.1:p.Val176Met
NP_001349106.1:p.Val106Met
NP_001393521.1:p.Val227Met
NP_001393522.1:p.Val227Met
NP_001393523.1:p.Val227Met
NP_001393524.1:p.Val227Met
NP_001393525.1:p.Val227Met
NP_001393526.1:p.Val227Met
NP_001393527.1:p.Val227Met
NP_001393528.1:p.Val227Met
NP_001393529.1:p.Val227Met
NP_001393530.1:p.Val227Met
NP_001393531.1:p.Val227Met
NP_001393532.1:p.Val227Met
NP_001393533.1:p.Val227Met
NP_001393534.1:p.Val227Met
NP_001393535.1:p.Val227Met
NP_001393536.1:p.Val227Met
NP_001393537.1:p.Val227Met
NP_001393538.1:p.Val227Met
NP_001393539.1:p.Val176Met
NP_001393540.1:p.Val176Met
NP_001393541.1:p.Val176Met
NP_001393542.1:p.Val176Met
NP_001393543.1:p.Val106Met
NP_001393544.1:p.Val106Met
NP_001393545.1:p.Val106Met
NP_001393546.1:p.Val106Met
NP_001393547.1:p.Val106Met
NP_001393548.1:p.Val106Met
NP_001393549.1:p.Val106Met
NP_001393550.1:p.Val106Met
NP_001393551.1:p.Val106Met
NP_001393552.1:p.Val106Met
NP_001393553.1:p.Val106Met
NP_001393554.1:p.Val106Met
LRG_486t1:c.679G>A
LRG_486:g.28213G>A
LRG_486p1:p.Val227Met
NC_000009.11:g.135796808C>T
NM_000368.3:c.679G>A
NM_000368.4:c.679G>A
NR_176214.1:n.896G>A
NR_176215.1:n.896G>A
NR_176216.1:n.763G>A
NR_176217.1:n.896G>A
NR_176218.1:n.896G>A

Protein change:

V106M

Molecular consequence:

NM_000368.5:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406592.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406593.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406594.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406595.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406596.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406597.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406598.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406599.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406600.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406601.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406602.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406603.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406604.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406605.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406606.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406607.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406608.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406609.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406610.1:c.526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406611.1:c.526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406612.1:c.526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406613.1:c.526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406614.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406615.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406616.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406617.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406618.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406619.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406620.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406621.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406622.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406623.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406624.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406625.1:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Tuberous sclerosis 1 (TSC1)
Identifiers:: MONDO: MONDO:0008612; MedGen: C1854465; Orphanet: 805; OMIM: 191100

Recent activity

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histone-lysine N-methyltransferase SETDB1 isoform X3 [Homo sapiens]
histone-lysine N-methyltransferase SETDB1 isoform X3 [Homo sapiens]
gi|2462515956|ref|XP_054195854.1|

Protein
PKP4-AS1 PKP4 antisense RNA 1 [Homo sapiens]
PKP4-AS1 PKP4 antisense RNA 1 [Homo sapiens]
Gene ID:100129029

Gene
100129029[uid] AND (alive[prop]) (1)
Gene
Avian paramyxovirus 1 isolate A373, complete genome
Avian paramyxovirus 1 isolate A373, complete genome
gi|1974981334|gb|MW342779.1|

Nucleotide
Coprinellus sp. voucher K:140930 18S ribosomal RNA gene, partial sequence; inter...
Coprinellus sp. voucher K:140930 18S ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 28S ribosomal RNA gene, partial sequence
gi|1653974345|gb|MK077827.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003341200	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 13, 2022)	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

SCV003341200

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 13, 2022)

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, SCV003341200.2

#	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 valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 227 of the TSC1 protein (p.Val227Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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