NM_004614.5(TK2):c.694G>C (p.Val232Leu) AND not provided

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:: RCV001872837.3

Allele description [Variation Report for NM_004614.5(TK2):c.694G>C (p.Val232Leu)]

NM_004614.5(TK2):c.694G>C (p.Val232Leu)

Gene:

TK2:thymidine kinase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q21

Genomic location:

Preferred name:

NM_004614.5(TK2):c.694G>C (p.Val232Leu)

HGVS:

NC_000016.10:g.66513736C>G
NG_016862.1:g.41677G>C
NM_001172643.1:c.601G>C
NM_001172644.2:c.619G>C
NM_001172645.2:c.640G>C
NM_001271934.2:c.547G>C
NM_001271935.1:c.432G>C
NM_001272050.2:c.403G>C
NM_004614.5:c.694G>CMANE SELECT
NP_001166114.1:p.Val201Leu
NP_001166115.1:p.Val207Leu
NP_001166116.1:p.Val214Leu
NP_001258863.1:p.Val183Leu
NP_001258864.1:p.Leu144=
NP_001258979.1:p.Val135Leu
NP_004605.4:p.Val232Leu
NC_000016.9:g.66547639C>G
NR_073520.2:n.1683G>C

Protein change:

V135L

Links:

dbSNP: rs576020835

NCBI 1000 Genomes Browser:

rs576020835

Molecular consequence:

NM_001172643.1:c.601G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001172644.2:c.619G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001172645.2:c.640G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001271934.2:c.547G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001272050.2:c.403G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004614.5:c.694G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_073520.2:n.1683G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001271935.1:c.432G>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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phospholipase A and acyltransferase 4 [Homo sapiens]
phospholipase A and acyltransferase 4 [Homo sapiens]
gi|149588791|ref|NP_004576.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002141425	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

SCV002141425

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, SCV002141425.2

#	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 leucine, which is neutral and non-polar, at codon 232 of the TK2 protein (p.Val232Leu). This variant is present in population databases (rs576020835, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with TK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1372242). 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 disruptive. 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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