NM_006790.3(MYOT):c.1118C>T (p.Ser373Leu) AND Myofibrillar myopathy 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 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:: RCV003086592.2

Allele description [Variation Report for NM_006790.3(MYOT):c.1118C>T (p.Ser373Leu)]

NM_006790.3(MYOT):c.1118C>T (p.Ser373Leu)

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.1118C>T (p.Ser373Leu)

HGVS:

NC_000005.10:g.137886141C>T
NG_008894.1:g.23286C>T
NM_001135940.2:c.566C>T
NM_001300911.2:c.773C>T
NM_006790.3:c.1118C>TMANE SELECT
NP_001129412.1:p.Ser189Leu
NP_001287840.1:p.Ser258Leu
NP_006781.1:p.Ser373Leu
NP_006781.1:p.Ser373Leu
LRG_201t1:c.1118C>T
LRG_201:g.23286C>T
LRG_201p1:p.Ser373Leu
NC_000005.9:g.137221830C>T
NM_006790.2:c.1118C>T

Protein change:

S189L

Molecular consequence:

NM_001135940.2:c.566C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001300911.2:c.773C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006790.3:c.1118C>T - 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
SCV003481451	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 2022)	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

SCV003481451

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 2022)

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, SCV003481451.2

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

Description

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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with MYOT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 373 of the MYOT protein (p.Ser373Leu).

#	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: Feb 20, 2024

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