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NM_000257.4(MYH7):c.3134G>T (p.Arg1045Leu) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 12, 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:
RCV002321503.10

Allele description [Variation Report for NM_000257.4(MYH7):c.3134G>T (p.Arg1045Leu)]

NM_000257.4(MYH7):c.3134G>T (p.Arg1045Leu)

Gene:
MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q11.2
Genomic location:
Preferred name:
NM_000257.4(MYH7):c.3134G>T (p.Arg1045Leu)
Other names:
NM_000257.4(MYH7):c.3134G>T
HGVS:
  • NC_000014.9:g.23422291C>A
  • NG_007884.1:g.18371G>T
  • NM_000257.4:c.3134G>TMANE SELECT
  • NP_000248.2:p.Arg1045Leu
  • LRG_384t1:c.3134G>T
  • LRG_384:g.18371G>T
  • NC_000014.8:g.23891500C>A
  • NM_000257.2:c.3134G>T
  • NM_000257.3:c.3134G>T
  • c.3134G>T
Protein change:
R1045L
Links:
dbSNP: rs397516178
NCBI 1000 Genomes Browser:
rs397516178
Molecular consequence:
  • NM_000257.4:c.3134G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002607568Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Likely pathogenic
(Dec 12, 2022)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL.

Genet Med. 2015 Nov;17(11):880-8. doi: 10.1038/gim.2014.205. Epub 2015 Jan 22. Erratum in: Genet Med. 2015 Apr;17(4):319. doi: 10.1038/gim.2015.16.

PubMed [citation]
PMID:
25611685

Phenotype-driven molecular autopsy for sudden cardiac death.

Cann F, Corbett M, O'Sullivan D, Tennant S, Hailey H, Grieve JH, Broadhurst P, Rankin R, Dean JC.

Clin Genet. 2017 Jan;91(1):22-29. doi: 10.1111/cge.12778. Epub 2016 May 11.

PubMed [citation]
PMID:
27000522
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002607568.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The p.R1045L variant (also known as c.3134G>T), located in coding exon 23 of the MYH7 gene, results from a G to T substitution at nucleotide position 3134. The arginine at codon 1045 is replaced by leucine, an amino acid with dissimilar properties. This variant was reported in numerous hypertrophic cardiomyopathy cohorts and has been reported to segregate with disease in several families (Alfares AA et al. Genet. Med., 2015 Nov;17:880-8; Walsh R et al. Genet. Med., 2017 02;19:192-203; Sheikh N et al. Circulation, 2018 Sep;138:1184-1194; GeneDx pers comm; Invitae pers comm; LMM pers comm; OMGL pers comm). An alternate amino acid substitution at this position, p.R1045C, has also been reported in HCM cases (Olivotto I et al. Mayo Clin. Proc., 2008 Jun;83:630-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2024