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NM_000257.4(MYH7):c.5422G>A (p.Gly1808Ser) AND Hypertrophic cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Mar 22, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000456307.12

Allele description [Variation Report for NM_000257.4(MYH7):c.5422G>A (p.Gly1808Ser)]

NM_000257.4(MYH7):c.5422G>A (p.Gly1808Ser)

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.5422G>A (p.Gly1808Ser)
Other names:
NM_000257.4(MYH7):c.5422G>A; p.Gly1808Ser
HGVS:
  • NC_000014.9:g.23415132C>T
  • NG_007884.1:g.25530G>A
  • NM_000257.4:c.5422G>AMANE SELECT
  • NP_000248.2:p.Gly1808Ser
  • LRG_384t1:c.5422G>A
  • LRG_384:g.25530G>A
  • NC_000014.8:g.23884341C>T
  • NM_000257.2:c.5422G>A
  • NM_000257.3:c.5422G>A
Protein change:
G1808S
Links:
dbSNP: rs369940645
NCBI 1000 Genomes Browser:
rs369940645
Molecular consequence:
  • NM_000257.4:c.5422G>A - 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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000546212Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jul 28, 2023)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001842659ClinGen Cardiomyopathy Variant Curation Expert Panel
reviewed by expert panel

(ClinGen CMP ACMG Specifications v1)
Uncertain significance
(Mar 22, 2021)
germlinecuration

Citation Link

Summary from all submissions

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

Citations

PubMed

Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.

Hershberger RE, Parks SB, Kushner JD, Li D, Ludwigsen S, Jakobs P, Nauman D, Burgess D, Partain J, Litt M.

Clin Transl Sci. 2008 May;1(1):21-6. doi: 10.1111/j.1752-8062.2008.00017.x.

PubMed [citation]
PMID:
19412328
PMCID:
PMC2633921

Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy.

Marsiglia JD, Credidio FL, de Oliveira TG, Reis RF, Antunes Mde O, de Araujo AQ, Pedrosa RP, Barbosa-Ferreira JM, Mady C, Krieger JE, Arteaga-Fernandez E, Pereira Ada C.

Am Heart J. 2013 Oct;166(4):775-82. doi: 10.1016/j.ahj.2013.07.029. Epub 2013 Sep 18.

PubMed [citation]
PMID:
24093860
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000546212.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. ClinVar contains an entry for this variant (Variation ID: 217468). This missense change has been observed in individuals with dilated cardiomyopathy and/or hypertrophic cardiomyopathy (PMID: 19412328, 24093860, 27247418, 34542152; Invitae). This variant is present in population databases (rs369940645, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1808 of the MYH7 protein (p.Gly1808Ser).

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

From ClinGen Cardiomyopathy Variant Curation Expert Panel, SCV001842659.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.5422G>A (p.Gly1808Ser) variant in MYH7 has been reported in 3 individuals with HCM (Marsiglia 2013 PMID:24093860; Homburger 2016 PMID:27247418; Invitae pers. comm.), 1 individual with unspecified cardiomyopathy (Invitae pers. comm.) and in 1 individual with sudden cardiac death (Campuzano 2017 PMID:28255936). This variant has also been identified in 0.0045% (FAF 95% CI, 4/30616) of South Asian chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). Since the MYH7 specifications state that PS4 is only applicable if the variant is absent or rare in large population studies, the PS4 criterion was not applied (Kelly 2018 PMID:29300372). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, due to a lack of sufficient evidence, this variant meets criteria to be classified as uncertain significance for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): None.

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

Last Updated: Jul 15, 2024