NM_000257.4(MYH7):c.4283T>C (p.Leu1428Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 14, 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:: RCV000618508.4

Allele description [Variation Report for NM_000257.4(MYH7):c.4283T>C (p.Leu1428Ser)]

NM_000257.4(MYH7):c.4283T>C (p.Leu1428Ser)

Genes:

MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
MHRT:myosin heavy chain associated RNA transcript [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_000257.4(MYH7):c.4283T>C (p.Leu1428Ser)

Other names:

p.L1428S:TTG>TCG; NM_000257.4(MYH7):c.4283T>C

HGVS:

NC_000014.9:g.23417573A>G
NG_007884.1:g.23089T>C
NM_000257.4:c.4283T>CMANE SELECT
NP_000248.2:p.Leu1428Ser
LRG_384t1:c.4283T>C
LRG_384:g.23089T>C
NC_000014.8:g.23886782A>G
NM_000257.2:c.4283T>C
NM_000257.3:c.4283T>C
NR_126491.1:n.854A>G

Protein change:

L1428S

Links:

dbSNP: rs727503244

NCBI 1000 Genomes Browser:

rs727503244

Molecular consequence:

NM_000257.4:c.4283T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.854A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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AGENCOURT_77726094 NICHD_XGC_skin_m Xenopus laevis cDNA clone IMAGE:8642058 5', ...
AGENCOURT_77726094 NICHD_XGC_skin_m Xenopus laevis cDNA clone IMAGE:8642058 5', mRNA sequence
gi|95017260|gnl|dbEST|39159426|gb|E 44.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000737035	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 14, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 20818890, 25611685, 26914223, 27247418, 27532257, 28606303, 33495597, 34542152 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000737035

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 14, 2022)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy.

Ho CY, López B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, Kwong R, González A, Colan SD, Seidman JG, Díez J, Seidman CE.

N Engl J Med. 2010 Aug 5;363(6):552-63. doi: 10.1056/NEJMoa1002659.

PubMed [citation]

PMID:: 20818890
PMCID:: PMC3049917

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

See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000737035.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

The p.L1428S variant (also known as c.4283T>C), located in coding exon 29 of the MYH7 gene, results from a T to C substitution at nucleotide position 4283. The leucine at codon 1428 is replaced by serine, an amino acid with dissimilar properties. This variant has been reported in a few hypertrophic cardiomyopathy cohorts; however, clinical details were limited (Ho CY et al. N. Engl. J. Med. 2010;363:552-63; Alfares AA et al. Genet. Med. 2015;17:880-8; Murphy SL et al. J Cardiovasc Transl Res. 2016;9:153-61). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 26, 2024

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