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NM_001018005.2(TPM1):c.256G>A (p.Ala86Thr) AND Dilated cardiomyopathy 1Y

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 21, 2020
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:
RCV001281081.2

Allele description [Variation Report for NM_001018005.2(TPM1):c.256G>A (p.Ala86Thr)]

NM_001018005.2(TPM1):c.256G>A (p.Ala86Thr)

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.256G>A (p.Ala86Thr)
HGVS:
  • NC_000015.10:g.63057000G>A
  • NG_007557.1:g.19362G>A
  • NM_000366.6:c.256G>A
  • NM_001018004.2:c.256G>A
  • NM_001018005.2:c.256G>AMANE SELECT
  • NM_001018006.2:c.256G>A
  • NM_001018007.2:c.256G>A
  • NM_001018008.2:c.148G>A
  • NM_001018020.2:c.256G>A
  • NM_001301244.2:c.256G>A
  • NM_001301289.2:c.148G>A
  • NM_001330344.2:c.148G>A
  • NM_001330346.2:c.148G>A
  • NM_001330351.2:c.148G>A
  • NM_001365776.1:c.256G>A
  • NM_001365777.1:c.256G>A
  • NM_001365778.1:c.382G>A
  • NM_001365779.1:c.256G>A
  • NM_001365780.1:c.148G>A
  • NM_001365781.2:c.148G>A
  • NM_001365782.1:c.148G>A
  • NP_000357.3:p.Ala86Thr
  • NP_001018004.1:p.Ala86Thr
  • NP_001018005.1:p.Ala86Thr
  • NP_001018006.1:p.Ala86Thr
  • NP_001018007.1:p.Ala86Thr
  • NP_001018008.1:p.Ala50Thr
  • NP_001018020.1:p.Ala86Thr
  • NP_001288173.1:p.Ala86Thr
  • NP_001288218.1:p.Ala50Thr
  • NP_001317273.1:p.Ala50Thr
  • NP_001317275.1:p.Ala50Thr
  • NP_001317280.1:p.Ala50Thr
  • NP_001352705.1:p.Ala86Thr
  • NP_001352706.1:p.Ala86Thr
  • NP_001352707.1:p.Ala128Thr
  • NP_001352708.1:p.Ala86Thr
  • NP_001352709.1:p.Ala50Thr
  • NP_001352710.1:p.Ala50Thr
  • NP_001352711.1:p.Ala50Thr
  • LRG_387t1:c.256G>A
  • LRG_387:g.19362G>A
  • LRG_387p1:p.Ala86Thr
  • NC_000015.9:g.63349199G>A
  • NM_001018005.1:c.256G>A
Protein change:
A128T
Links:
dbSNP: rs2034911718
NCBI 1000 Genomes Browser:
rs2034911718
Molecular consequence:
  • NM_000366.6:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018004.2:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018005.2:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018006.2:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018007.2:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018008.2:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018020.2:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301244.2:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301289.2:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330344.2:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330346.2:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330351.2:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365776.1:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365777.1:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365778.1:c.382G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365779.1:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365780.1:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365781.2:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365782.1:c.148G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Dilated cardiomyopathy 1Y (CMD1Y)
Identifiers:
MONDO: MONDO:0012744; MedGen: C2678476; Orphanet: 154; Orphanet: 54260; OMIM: 611878

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001451437Institute of Human Genetics, University of Goettingen
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Dec 21, 2020) 		unknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

A fast and cost-effective molecular diagnostic tool for genetic diseases involved in sudden cardiac death.

Chanavat V, Janin A, Millat G.

Clin Chim Acta. 2016 Jan 30;453:80-5. doi: 10.1016/j.cca.2015.12.011. Epub 2015 Dec 10.

PubMed [citation]
PMID:
26688388

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 Institute of Human Genetics, University of Goettingen, SCV001451437.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (2)

Description

The variant c.256G>A (p.(Ala86Thr)) in exon 3 of the TPM1-gene is not found in known databases (ExAC or gnomAD) and it has been published in the literature as a variant of unknown significance (PMID: 26688388). Another nucleotide change resulting in another amino acid change at the same position was described as pathogenic (c.257C>T, p.(Ala86Val); PMID: 31568572). The variant affects a highly conserved nucleotide, a highly conserved amino acid, there is a small physicochemical difference between Ala and Thr and the variant is located within a protein domain (Tropomyosin). This variant has a pathogenic computational verdict based on in silico prediction programs. Missense variants in TPM1 are a known mechanism of disease. Thus, we consider this TPM1-variant a likely pathogenic variant. ACMG criteria used for classification: PM1, PM2, PM5, PP2, PP3.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Mar 4, 2023