NM_000257.4(MYH7):c.835G>A (p.Ala279Thr) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 15, 2019
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:: RCV000036006.7

Allele description [Variation Report for NM_000257.4(MYH7):c.835G>A (p.Ala279Thr)]

NM_000257.4(MYH7):c.835G>A (p.Ala279Thr)

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.835G>A (p.Ala279Thr)

HGVS:

NC_000014.9:g.23430961C>T
NG_007884.1:g.9701G>A
NM_000257.4:c.835G>AMANE SELECT
NP_000248.2:p.Ala279Thr
LRG_384t1:c.835G>A
LRG_384:g.9701G>A
NC_000014.8:g.23900170C>T
NM_000257.2:c.835G>A
c.835G>A

Protein change:

A279T

Links:

dbSNP: rs397516270

NCBI 1000 Genomes Browser:

rs397516270

Molecular consequence:

NM_000257.4:c.835G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Chain F, 60S ribosomal protein L34
Chain F, 60S ribosomal protein L34
gi|2559883547|pdb|8INF|F

Protein
Chain q, 60S ribosomal protein L10a
Chain q, 60S ribosomal protein L10a
gi|2559883534|pdb|8INF|q

Protein
Chain X, 60S ribosomal protein L37a
Chain X, 60S ribosomal protein L37a
gi|2559883562|pdb|8INF|X

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000059658	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Aug 15, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24503780, 27532257, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059658

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Aug 15, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	5	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059658.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (3)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Ala279Thr variant in MYH7 has been in 1 individual with DCM and segregated with disease in 4 affected family members (LMM data, Pugh 2014, Walsh 2017). It was absent from large population studies. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. Of note, this variant lies in the head region of the protein and missense variants in this region are statistically more likely to be disease-associated (Walsh 2017). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM1, PM2, PP1.

#	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		5	not provided	1	not provided

Last Updated: Dec 24, 2022

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