NM_000368.5(TSC1):c.1282_1283delinsCT (p.Ala428Leu) AND Tuberous sclerosis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 28, 2023
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:: RCV001040743.7

Allele description [Variation Report for NM_000368.5(TSC1):c.1282_1283delinsCT (p.Ala428Leu)]

NM_000368.5(TSC1):c.1282_1283delinsCT (p.Ala428Leu)

Gene:

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

Variant type:

Indel

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_000368.5(TSC1):c.1282_1283delinsCT (p.Ala428Leu)

HGVS:

NC_000009.12:g.132907351_132907352delinsAG
NG_012386.1:g.42282_42283delinsCT
NM_000368.5:c.1282_1283delinsCTMANE SELECT
NM_001162426.2:c.1279_1280delinsCT
NM_001162427.2:c.1129_1130delinsCT
NM_001362177.2:c.919_920delinsCT
NP_000359.1:p.Ala428Leu
NP_000359.1:p.Ala428Leu
NP_001155898.1:p.Ala427Leu
NP_001155899.1:p.Ala377Leu
NP_001349106.1:p.Ala307Leu
LRG_486t1:c.1282_1283delinsCT
LRG_486:g.42282_42283delinsCT
LRG_486p1:p.Ala428Leu
NC_000009.11:g.135782738_135782739delinsAG
NM_000368.4:c.1282_1283delGCinsCT
NM_000368.4:c.1282_1283delinsCT

Protein change:

A307L

Links:

dbSNP: rs587778721

NCBI 1000 Genomes Browser:

rs587778721

Molecular consequence:

NM_000368.5:c.1282_1283delinsCT - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.1279_1280delinsCT - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.1129_1130delinsCT - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.919_920delinsCT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001204332	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 28, 2023)	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

SCV001204332

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 28, 2023)

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, SCV001204332.5

#	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 alanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 428 of the TSC1 protein (p.Ala428Leu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with TSC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 135362). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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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