NM_000368.5(TSC1):c.1995C>A (p.Asn665Lys) AND Tuberous sclerosis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 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:: RCV002815577.3

Allele description [Variation Report for NM_000368.5(TSC1):c.1995C>A (p.Asn665Lys)]

NM_000368.5(TSC1):c.1995C>A (p.Asn665Lys)

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.1995C>A (p.Asn665Lys)

HGVS:

NC_000009.12:g.132905583G>T
NG_012386.1:g.44051C>A
NM_000368.5:c.1995C>AMANE SELECT
NM_001162426.2:c.1992C>A
NM_001162427.2:c.1842C>A
NM_001362177.2:c.1632C>A
NM_001406592.1:c.1995C>A
NM_001406593.1:c.1995C>A
NM_001406594.1:c.1995C>A
NM_001406595.1:c.1995C>A
NM_001406596.1:c.1995C>A
NM_001406597.1:c.1992C>A
NM_001406598.1:c.1992C>A
NM_001406599.1:c.1992C>A
NM_001406600.1:c.1992C>A
NM_001406601.1:c.1995C>A
NM_001406602.1:c.1995C>A
NM_001406603.1:c.1992C>A
NM_001406604.1:c.1992C>A
NM_001406605.1:c.1995C>A
NM_001406606.1:c.1995C>A
NM_001406607.1:c.1995C>A
NM_001406608.1:c.1992C>A
NM_001406609.1:c.1992C>A
NM_001406610.1:c.1842C>A
NM_001406611.1:c.1839C>A
NM_001406612.1:c.1839C>A
NM_001406613.1:c.1839C>A
NM_001406614.1:c.1632C>A
NM_001406615.1:c.1632C>A
NM_001406616.1:c.1632C>A
NM_001406617.1:c.1632C>A
NM_001406618.1:c.1632C>A
NM_001406619.1:c.1632C>A
NM_001406620.1:c.1629C>A
NM_001406621.1:c.1629C>A
NM_001406622.1:c.1629C>A
NM_001406623.1:c.1629C>A
NM_001406624.1:c.1632C>A
NM_001406625.1:c.1629C>A
NM_001406626.1:c.1044C>A
NM_001406627.1:c.1041C>A
NM_001406628.1:c.1041C>A
NM_001406629.1:c.942C>A
NM_001406630.1:c.942C>A
NP_000359.1:p.Asn665Lys
NP_000359.1:p.Asn665Lys
NP_000359.1:p.Asn665Lys
NP_001155898.1:p.Asn664Lys
NP_001155899.1:p.Asn614Lys
NP_001349106.1:p.Asn544Lys
NP_001393521.1:p.Asn665Lys
NP_001393522.1:p.Asn665Lys
NP_001393523.1:p.Asn665Lys
NP_001393524.1:p.Asn665Lys
NP_001393525.1:p.Asn665Lys
NP_001393526.1:p.Asn664Lys
NP_001393527.1:p.Asn664Lys
NP_001393528.1:p.Asn664Lys
NP_001393529.1:p.Asn664Lys
NP_001393530.1:p.Asn665Lys
NP_001393531.1:p.Asn665Lys
NP_001393532.1:p.Asn664Lys
NP_001393533.1:p.Asn664Lys
NP_001393534.1:p.Asn665Lys
NP_001393535.1:p.Asn665Lys
NP_001393536.1:p.Asn665Lys
NP_001393537.1:p.Asn664Lys
NP_001393538.1:p.Asn664Lys
NP_001393539.1:p.Asn614Lys
NP_001393540.1:p.Asn613Lys
NP_001393541.1:p.Asn613Lys
NP_001393542.1:p.Asn613Lys
NP_001393543.1:p.Asn544Lys
NP_001393544.1:p.Asn544Lys
NP_001393545.1:p.Asn544Lys
NP_001393546.1:p.Asn544Lys
NP_001393547.1:p.Asn544Lys
NP_001393548.1:p.Asn544Lys
NP_001393549.1:p.Asn543Lys
NP_001393550.1:p.Asn543Lys
NP_001393551.1:p.Asn543Lys
NP_001393552.1:p.Asn543Lys
NP_001393553.1:p.Asn544Lys
NP_001393554.1:p.Asn543Lys
NP_001393555.1:p.Asn348Lys
NP_001393556.1:p.Asn347Lys
NP_001393557.1:p.Asn347Lys
NP_001393558.1:p.Asn314Lys
NP_001393559.1:p.Asn314Lys
LRG_486t1:c.1995C>A
LRG_486:g.44051C>A
LRG_486p1:p.Asn665Lys
NC_000009.11:g.135780970G>T
NM_000368.3:c.1995C>A
NM_000368.4:c.1995C>A
NR_176214.1:n.2212C>A
NR_176215.1:n.2212C>A
NR_176216.1:n.2079C>A
NR_176217.1:n.2209C>A
NR_176218.1:n.2212C>A

Protein change:

N314K

Molecular consequence:

NM_000368.5:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.1842C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406592.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406593.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406594.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406595.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406596.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406597.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406598.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406599.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406600.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406601.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406602.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406603.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406604.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406605.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406606.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406607.1:c.1995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406608.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406609.1:c.1992C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406610.1:c.1842C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406611.1:c.1839C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406612.1:c.1839C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406613.1:c.1839C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406614.1:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406615.1:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406616.1:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406617.1:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406618.1:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406619.1:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406620.1:c.1629C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406621.1:c.1629C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406622.1:c.1629C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406623.1:c.1629C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406624.1:c.1632C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406625.1:c.1629C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406626.1:c.1044C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406627.1:c.1041C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406628.1:c.1041C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406629.1:c.942C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406630.1:c.942C>A - 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
SCV003207739	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 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

SCV003207739

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 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, SCV003207739.2

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TSC1-related conditions. This variant is present in population databases (rs748733167, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 665 of the TSC1 protein (p.Asn665Lys).

#	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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