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NM_001018005.2(TPM1):c.712C>T (p.Arg238Trp) AND not specified

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 27, 2013
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000036356.7

Allele description [Variation Report for NM_001018005.2(TPM1):c.712C>T (p.Arg238Trp)]

NM_001018005.2(TPM1):c.712C>T (p.Arg238Trp)

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.712C>T (p.Arg238Trp)
Other names:
p.R238W:CGG>TGG
HGVS:
  • NC_000015.10:g.63062585C>T
  • NG_007557.1:g.24947C>T
  • NM_000366.6:c.712C>T
  • NM_001018004.2:c.712C>T
  • NM_001018005.2:c.712C>TMANE SELECT
  • NM_001018006.2:c.712C>T
  • NM_001018007.2:c.712C>T
  • NM_001018008.2:c.604C>T
  • NM_001018020.2:c.712C>T
  • NM_001301244.2:c.712C>T
  • NM_001301289.2:c.604C>T
  • NM_001330344.2:c.604C>T
  • NM_001330346.2:c.604C>T
  • NM_001330351.2:c.604C>T
  • NM_001365776.1:c.712C>T
  • NM_001365777.1:c.712C>T
  • NM_001365778.1:c.838C>T
  • NM_001365779.1:c.712C>T
  • NM_001365780.1:c.604C>T
  • NM_001365781.2:c.604C>T
  • NM_001365782.1:c.604C>T
  • NP_000357.3:p.Arg238Trp
  • NP_001018004.1:p.Arg238Trp
  • NP_001018005.1:p.Arg238Trp
  • NP_001018006.1:p.Arg238Trp
  • NP_001018007.1:p.Arg238Trp
  • NP_001018008.1:p.Arg202Trp
  • NP_001018020.1:p.Arg238Trp
  • NP_001288173.1:p.Arg238Trp
  • NP_001288218.1:p.Arg202Trp
  • NP_001317273.1:p.Arg202Trp
  • NP_001317275.1:p.Arg202Trp
  • NP_001317280.1:p.Arg202Trp
  • NP_001352705.1:p.Arg238Trp
  • NP_001352706.1:p.Arg238Trp
  • NP_001352707.1:p.Arg280Trp
  • NP_001352708.1:p.Arg238Trp
  • NP_001352709.1:p.Arg202Trp
  • NP_001352710.1:p.Arg202Trp
  • NP_001352711.1:p.Arg202Trp
  • LRG_387t1:c.712C>T
  • LRG_387:g.24947C>T
  • LRG_387p1:p.Arg238Trp
  • NC_000015.9:g.63354784C>T
  • NM_000366.5:c.712C>T
  • NM_001018005.1:c.712C>T
  • c.712C>T
Protein change:
R202W
Links:
dbSNP: rs397516386
NCBI 1000 Genomes Browser:
rs397516386
Molecular consequence:
  • NM_000366.6:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018004.2:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018005.2:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018006.2:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018007.2:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018008.2:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018020.2:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301244.2:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301289.2:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330344.2:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330346.2:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330351.2:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365776.1:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365777.1:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365778.1:c.838C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365779.1:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365780.1:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365781.2:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365782.1:c.604C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000060008Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
no assertion criteria provided
Uncertain significance
(Mar 1, 2008) 		germlineclinical testing

SCV000280544Stanford Center for Inherited Cardiovascular Disease, Stanford University
no assertion criteria provided
Uncertain significance
(May 27, 2013) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided31not providednot providednot providedclinical testing

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060008.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000280544.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided

Description

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Arg238Trp (R238W; c.712 C>T) in exon 8 of the TPM1 gene The testing lab refered to it as “published” because after being seen at LMM it was added to a DCM sequencing chip in a publication by Zimmerman et al. (2010) as a “pathogenic variant” (this is the group from LMM and Partners Healthcare; see the paper’s supplementary material). Because of this same reference, it is listed in HGMD. There is no segregation data available. This is a non-conservative amino acid change, resulting in the replacement of a positively-charged Arginine with a nonpolar Tryptophan. The Arginine at this location is highly conserved across 10 vertebrate species for which information is available. Several adjacent residues on either side are also highly conserved. Variation at nearby residues has been associated with cardiomyopathy, which supports the functional importance of this region of the protein: Asp230Asn, Ala239Thr (HGMD professional version as of January 17, 2014). In silico analysis with PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/) predicts the variant to be “probably damaging” with a score of 1.0. In total the variant has not been seen in ~6500 individuals from publicly available population datasets. This variant is not listed in the NHLBI Exome Sequencing Project dataset (http://evs.gs.washington.edu/EVS/), which currently includes variant calls on ~4300 Caucasian and ~2200 African American individuals. However, these individuals are not ancestry-matched to our patient, who is of Mexican descent. The phenotype of the ESP individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. There is also no variation at this codon listed in dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP) or 1000 genomes (http://browser.1000genomes.org/index.htm) as of April 15, 2014.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not providednot providednot provided

Last Updated: Jun 23, 2024