NM_005159.5(ACTC1):c.275_277del (p.Phe92del) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Mar 27, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_005159.5(ACTC1):c.275_277del (p.Phe92del)]

NM_005159.5(ACTC1):c.275_277del (p.Phe92del)

GJD2-DT:GJD2 divergent transcript [Gene - HGNC]
ACTC1:actin alpha cardiac muscle 1 [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_005159.5(ACTC1):c.275_277del (p.Phe92del)
  • NC_000015.10:g.34793424_34793426del
  • NG_007553.1:g.7303_7305del
  • NM_005159.5:c.275_277delMANE SELECT
  • NP_005150.1:p.Phe92del
  • LRG_388t1:c.275_277del
  • LRG_388:g.7303_7305del
  • NC_000015.9:g.35085625_35085627del
  • NM_005159.4:c.275_277del
  • NM_005159.4:c.275_277delTCT
  • p.F92del
Protein change:
dbSNP: rs730880388
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_005159.5:c.275_277del - inframe_deletion - [Sequence Ontology: SO:0001822]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000207703GeneDxcriteria provided, single submitter
Likely pathogenic
(Mar 27, 2019)
germlineclinical testing

Citation Link,

SCV000280035Stanford Center for Inherited Cardiovascular Disease, Stanford Universityno assertion criteria providedLikely pathogenic
(Dec 3, 2014)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided2not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000207703.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 20031618, 31481237)

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000280035.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided


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. We classify this variant as likely disease-causing. This variant has been previously reported in 1 pre-adolescent individual with HCM (Kaski et al. 2009). There is no published segregation data. This is a deletion of an entire amino acid. The Phenylalanine at this location is absolutely conserved across 100 vertebrate species. The surrounding residues are also very highly conserved. This is the only single amino acid deletion in ACTC1 listed in HGMD as of January 2014. Variation at the following nearby residues have been reported in the HGMD to be associated with HCM: His90Tyr, Arg97Cys, Glu101Lys. This supports the functional importance of this region of the protein. It has not been seen in 6700 individuals from control groups or publicly available population datasets. Kaski et al. (2009) report that it was absent from 200 control individuals. It is also absent from ~6500 individuals of European and African-American ancestry in the NHLBI Exome Sequencing Project. In fact, there is no protein variation in ACTC1 listed in ESP within 100 amino acids of this location, which points to how little variation is typically found in this protein (http://evs.gs.washington.edu/EVS/). There is no variation at this codon listed in 1000 genomes. There is also no variant listed in 1000 genomes that alters an amino acid in ACTC1 as of December 3, 2014.

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

Last Updated: Nov 27, 2021

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