NM_001018005.2(TPM1):c.262C>G (p.Leu88Val) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 16, 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:: RCV000560434.8

Allele description [Variation Report for NM_001018005.2(TPM1):c.262C>G (p.Leu88Val)]

NM_001018005.2(TPM1):c.262C>G (p.Leu88Val)

Gene:

TPM1:tropomyosin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q22.2

Genomic location:

Preferred name:

NM_001018005.2(TPM1):c.262C>G (p.Leu88Val)

HGVS:

NC_000015.10:g.63057006C>G
NG_007557.1:g.19368C>G
NM_000366.6:c.262C>G
NM_001018004.2:c.262C>G
NM_001018005.2:c.262C>GMANE SELECT
NM_001018006.2:c.262C>G
NM_001018007.2:c.262C>G
NM_001018008.2:c.154C>G
NM_001018020.2:c.262C>G
NM_001301244.2:c.262C>G
NM_001301289.2:c.154C>G
NM_001330344.2:c.154C>G
NM_001330346.2:c.154C>G
NM_001330351.2:c.154C>G
NM_001365776.1:c.262C>G
NM_001365777.1:c.262C>G
NM_001365778.1:c.388C>G
NM_001365779.1:c.262C>G
NM_001365780.1:c.154C>G
NM_001365781.2:c.154C>G
NM_001365782.1:c.154C>G
NP_000357.3:p.Leu88Val
NP_001018004.1:p.Leu88Val
NP_001018005.1:p.Leu88Val
NP_001018006.1:p.Leu88Val
NP_001018007.1:p.Leu88Val
NP_001018008.1:p.Leu52Val
NP_001018020.1:p.Leu88Val
NP_001288173.1:p.Leu88Val
NP_001288218.1:p.Leu52Val
NP_001317273.1:p.Leu52Val
NP_001317275.1:p.Leu52Val
NP_001317280.1:p.Leu52Val
NP_001352705.1:p.Leu88Val
NP_001352706.1:p.Leu88Val
NP_001352707.1:p.Leu130Val
NP_001352708.1:p.Leu88Val
NP_001352709.1:p.Leu52Val
NP_001352710.1:p.Leu52Val
NP_001352711.1:p.Leu52Val
LRG_387t1:c.262C>G
LRG_387:g.19368C>G
LRG_387p1:p.Leu88Val
NC_000015.9:g.63349205C>G
NM_001018005.1:c.262C>G

Protein change:

L130V

Links:

dbSNP: rs1555407795

NCBI 1000 Genomes Browser:

rs1555407795

Molecular consequence:

NM_000366.6:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018004.2:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018005.2:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018006.2:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018007.2:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018008.2:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018020.2:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301244.2:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301289.2:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330344.2:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330346.2:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330351.2:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365776.1:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365777.1:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365778.1:c.388C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365779.1:c.262C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365780.1:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365781.2:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365782.1:c.154C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000623801	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21310275, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000623801

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.

Jordan DM, Kiezun A, Baxter SM, Agarwala V, Green RC, Murray MF, Pugh T, Lebo MS, Rehm HL, Funke BH, Sunyaev SR.

Am J Hum Genet. 2011 Feb 11;88(2):183-92. doi: 10.1016/j.ajhg.2011.01.011.

PubMed [citation]

PMID:: 21310275
PMCID:: PMC3035712

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, SCV000623801.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. An algorithm developed specifically for the TPM1 gene suggests that this missense change is likely to be deleterious (PMID: 21310275). ClinVar contains an entry for this variant (Variation ID: 454418). This missense change has been observed in individual(s) with TPM1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 88 of the TPM1 protein (p.Leu88Val).

#	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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