NM_001378030.1(CCDC78):c.811C>T (p.Arg271Trp) AND Congenital myopathy with internal nuclei and atypical cores

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 31, 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:: RCV000985186.6

Allele description [Variation Report for NM_001378030.1(CCDC78):c.811C>T (p.Arg271Trp)]

NM_001378030.1(CCDC78):c.811C>T (p.Arg271Trp)

Gene:

CCDC78:coiled-coil domain containing 78 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_001378030.1(CCDC78):c.811C>T (p.Arg271Trp)

HGVS:

NC_000016.10:g.724464G>A
NG_032932.1:g.7010C>T
NM_001031737.3:c.811C>T
NM_001378030.1:c.811C>TMANE SELECT
NM_001378031.1:c.811C>T
NM_001378033.1:c.244C>T
NP_001026907.2:p.Arg271Trp
NP_001364959.1:p.Arg271Trp
NP_001364960.1:p.Arg271Trp
NP_001364962.1:p.Arg82Trp
LRG_705t1:c.811C>T
LRG_705t2:c.811C>T
LRG_705:g.7010C>T
LRG_705p1:p.Arg271Trp
LRG_705p2:p.Arg271Trp
NC_000016.9:g.774464G>A
NC_000016.9:g.774464G>A
NM_001031737.2:c.811C>T
NR_165382.1:n.1368C>T
NR_165383.1:n.1014C>T
NR_165384.1:n.979C>T
NR_165385.1:n.1079C>T
NR_165386.1:n.1146C>T

Protein change:

R271W

Links:

dbSNP: rs200865845

NCBI 1000 Genomes Browser:

rs200865845

Molecular consequence:

NM_001031737.3:c.811C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378030.1:c.811C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378031.1:c.811C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378033.1:c.244C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_165382.1:n.1368C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165383.1:n.1014C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165384.1:n.979C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165385.1:n.1079C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165386.1:n.1146C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Congenital myopathy with internal nuclei and atypical cores
Synonyms:: Myopathy, centronuclear, 4
Identifiers:: MONDO: MONDO:0013890; MedGen: C4707232; OMIM: 614807

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001133201	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Likely pathogenic (Sep 26, 2019)	germline	clinical testing
SCV002304388	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 31, 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

SCV001133201

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

no assertion criteria provided

Likely pathogenic
(Sep 26, 2019)

germline

clinical testing

SCV002304388

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 31, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV001133201.1

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

#	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

From Invitae, SCV002304388.3

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CCDC78 protein function. ClinVar contains an entry for this variant (Variation ID: 800966). This variant has not been reported in the literature in individuals affected with CCDC78-related conditions. This variant is present in population databases (rs200865845, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 271 of the CCDC78 protein (p.Arg271Trp).

#	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

ClinVar

Relating variation to medicine