NM_001018005.2(TPM1):c.413A>C (p.Glu138Ala) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 9, 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:: RCV002568911.4

Allele description [Variation Report for NM_001018005.2(TPM1):c.413A>C (p.Glu138Ala)]

NM_001018005.2(TPM1):c.413A>C (p.Glu138Ala)

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.413A>C (p.Glu138Ala)

HGVS:

NC_000015.10:g.63059601A>C
NG_007557.1:g.21963A>C
NM_000366.6:c.413A>C
NM_001018004.2:c.413A>C
NM_001018005.2:c.413A>CMANE SELECT
NM_001018006.2:c.413A>C
NM_001018007.2:c.413A>C
NM_001018008.2:c.305A>C
NM_001018020.2:c.413A>C
NM_001301244.2:c.413A>C
NM_001301289.2:c.305A>C
NM_001330344.2:c.305A>C
NM_001330346.2:c.305A>C
NM_001330351.2:c.305A>C
NM_001365776.1:c.413A>C
NM_001365777.1:c.413A>C
NM_001365778.1:c.539A>C
NM_001365779.1:c.413A>C
NM_001365780.1:c.305A>C
NM_001365781.2:c.305A>C
NM_001365782.1:c.305A>C
NP_000357.3:p.Glu138Ala
NP_001018004.1:p.Glu138Ala
NP_001018005.1:p.Glu138Ala
NP_001018006.1:p.Glu138Ala
NP_001018007.1:p.Glu138Ala
NP_001018008.1:p.Glu102Ala
NP_001018020.1:p.Glu138Ala
NP_001288173.1:p.Glu138Ala
NP_001288218.1:p.Glu102Ala
NP_001317273.1:p.Glu102Ala
NP_001317275.1:p.Glu102Ala
NP_001317280.1:p.Glu102Ala
NP_001352705.1:p.Glu138Ala
NP_001352706.1:p.Glu138Ala
NP_001352707.1:p.Glu180Ala
NP_001352708.1:p.Glu138Ala
NP_001352709.1:p.Glu102Ala
NP_001352710.1:p.Glu102Ala
NP_001352711.1:p.Glu102Ala
LRG_387t1:c.413A>C
LRG_387:g.21963A>C
LRG_387p1:p.Glu138Ala
NC_000015.9:g.63351800A>C

Protein change:

E102A

Links:

dbSNP: rs786204410

NCBI 1000 Genomes Browser:

rs786204410

Molecular consequence:

NM_000366.6:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001018004.2:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001018005.2:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001018006.2:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001018007.2:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001018008.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001018020.2:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001301244.2:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001301289.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330344.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330346.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330351.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365776.1:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365777.1:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365778.1:c.539A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365779.1:c.413A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365780.1:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365781.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365782.1:c.305A>C - 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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CCB57068.1 (0)
Protein
Mycobacterium avium subsp. hominissuis 10-5606 contig001196, whole genome shotgu...
Mycobacterium avium subsp. hominissuis 10-5606 contig001196, whole genome shotgun sequence
gi|564196825|gb|AYNU01001196.1||gnl AYNU01|contig001196

Nucleotide
TSA: Spodoptera frugiperda SF21Tr870 transcribed RNA sequence
TSA: Spodoptera frugiperda SF21Tr870 transcribed RNA sequence
gi|919298167|gb|GCTM01000869.1||gnl GCTM01|SF21Tr870

Nucleotide
TSA: Spodoptera frugiperda SF21Tr843 transcribed RNA sequence
TSA: Spodoptera frugiperda SF21Tr843 transcribed RNA sequence
gi|919298202|gb|GCTM01000842.1||gnl GCTM01|SF21Tr843

Nucleotide
TSA: Spodoptera frugiperda SF21Tr819 transcribed RNA sequence
TSA: Spodoptera frugiperda SF21Tr819 transcribed RNA sequence
gi|919298235|gb|GCTM01000818.1||gnl GCTM01|SF21Tr819

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003219464	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 9, 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

SCV003219464

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 9, 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, SCV003219464.2

#	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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1176994). This variant has not been reported in the literature in individuals affected with TPM1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 138 of the TPM1 protein (p.Glu138Ala).

#	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: Oct 20, 2024

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