NM_002470.4(MYH3):c.2621T>C (p.Leu874Pro) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 18, 2015
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:: RCV000479373.1

Allele description [Variation Report for NM_002470.4(MYH3):c.2621T>C (p.Leu874Pro)]

NM_002470.4(MYH3):c.2621T>C (p.Leu874Pro)

Gene:

MYH3:myosin heavy chain 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_002470.4(MYH3):c.2621T>C (p.Leu874Pro)

HGVS:

NC_000017.11:g.10640057A>G
NG_011537.1:g.22242T>C
NM_002470.4:c.2621T>CMANE SELECT
NP_002461.2:p.Leu874Pro
NC_000017.10:g.10543374A>G
NM_002470.3:c.2621T>C

Protein change:

L874P

Links:

dbSNP: rs1064793203

NCBI 1000 Genomes Browser:

rs1064793203

Molecular consequence:

NM_002470.4:c.2621T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000565281	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Aug 18, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000565281

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Aug 18, 2015)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000565281.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The L874P variant in the MYH3 gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The L874P variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L874P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret L874P as a strong candidate for a disease-causing variant; however, the possibility it may be a rare benign variant cannot be excluded.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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