NM_006790.3(MYOT):c.1442G>A (p.Gly481Glu) AND Myofibrillar myopathy 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 26, 2020
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:: RCV001348614.6

Allele description [Variation Report for NM_006790.3(MYOT):c.1442G>A (p.Gly481Glu)]

NM_006790.3(MYOT):c.1442G>A (p.Gly481Glu)

Genes:

PKD2L2-DT:PKD2L2 divergent transcript [Gene - HGNC]
MYOT:myotilin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.2

Genomic location:

Preferred name:

NM_006790.3(MYOT):c.1442G>A (p.Gly481Glu)

HGVS:

NC_000005.10:g.137887330G>A
NG_008894.1:g.24475G>A
NM_001135940.2:c.890G>A
NM_001300911.2:c.1097G>A
NM_006790.3:c.1442G>AMANE SELECT
NP_001129412.1:p.Gly297Glu
NP_001287840.1:p.Gly366Glu
NP_006781.1:p.Gly481Glu
LRG_201:g.24475G>A
NC_000005.9:g.137223019G>A

Protein change:

G297E

Links:

dbSNP: rs766736443

NCBI 1000 Genomes Browser:

rs766736443

Molecular consequence:

NM_001135940.2:c.890G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300911.2:c.1097G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006790.3:c.1442G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Myofibrillar myopathy 3 (MFM3)
Synonyms:: Limb-girdle muscular dystrophy, type 1A; Muscular dystrophy, proximal, type 1A; Spheroid body myopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012215; MedGen: C3714934; Orphanet: 266; Orphanet: 268129; OMIM: 609200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001542921	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001542921

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 26, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001542921.4

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

Description

This sequence change replaces glycine with glutamic acid at codon 481 of the MYOT protein (p.Gly481Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYOT-related conditions. This variant is present in population databases (rs766736443, ExAC 0.006%).

#	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: Mar 5, 2024

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