NM_000368.5(TSC1):c.518C>T (p.Ala173Val) AND Tuberous sclerosis 1

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Oct 2, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000641975.17

Allele description [Variation Report for NM_000368.5(TSC1):c.518C>T (p.Ala173Val)]

NM_000368.5(TSC1):c.518C>T (p.Ala173Val)

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.518C>T (p.Ala173Val)

HGVS:

NC_000009.12:g.132921964G>A
NG_012386.1:g.27670C>T
NM_000368.5:c.518C>TMANE SELECT
NM_001162426.2:c.518C>T
NM_001162427.2:c.365C>T
NM_001362177.2:c.155C>T
NP_000359.1:p.Ala173Val
NP_000359.1:p.Ala173Val
NP_001155898.1:p.Ala173Val
NP_001155899.1:p.Ala122Val
NP_001349106.1:p.Ala52Val
LRG_486t1:c.518C>T
LRG_486:g.27670C>T
LRG_486p1:p.Ala173Val
NC_000009.11:g.135797351G>A
NM_000368.4:c.518C>T

Protein change:

A122V

Links:

dbSNP: rs777484049

NCBI 1000 Genomes Browser:

rs777484049

Molecular consequence:

NM_000368.5:c.518C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162426.2:c.518C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001162427.2:c.365C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001362177.2:c.155C>T - 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
SCV000763627	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Oct 2, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002040162	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005406022	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely benign (Aug 23, 2024)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000763627

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Oct 2, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002040162

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Nov 7, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005406022

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely benign
(Aug 23, 2024)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000763627.10

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

#	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

From Genome-Nilou Lab, SCV002040162.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV005406022.1

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

Description

This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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