NM_001378030.1(CCDC78):c.1112del (p.Gln371fs) AND Congenital myopathy with internal nuclei and atypical cores

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 26, 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:: RCV001039806.5

Allele description [Variation Report for NM_001378030.1(CCDC78):c.1112del (p.Gln371fs)]

NM_001378030.1(CCDC78):c.1112del (p.Gln371fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_001378030.1(CCDC78):c.1112del (p.Gln371fs)

HGVS:

NC_000016.10:g.723878del
NG_032932.1:g.7596del
NM_001031737.3:c.1112del
NM_001378030.1:c.1112delMANE SELECT
NM_001378031.1:c.953+444del
NM_001378033.1:c.545del
NP_001026907.2:p.Gln371fs
NP_001364959.1:p.Gln371fs
NP_001364962.1:p.Gln182fs
LRG_705t1:c.1112del
LRG_705t2:c.1112del
LRG_705:g.7596del
LRG_705p1:p.Gln371fs
LRG_705p2:p.Gln371fs
NC_000016.9:g.773878del
NM_001031737.2:c.1112del
NM_001031737.2:c.1112delA
NR_165382.1:n.1669del
NR_165383.1:n.1315del
NR_165384.1:n.1280del
NR_165385.1:n.1380del
NR_165386.1:n.1447del

Protein change:

Q182fs

Links:

dbSNP: rs765483630

NCBI 1000 Genomes Browser:

rs765483630

Molecular consequence:

NM_001031737.3:c.1112del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378030.1:c.1112del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378033.1:c.545del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378031.1:c.953+444del - intron variant - [Sequence Ontology: SO:0001627]
NR_165382.1:n.1669del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165383.1:n.1315del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165384.1:n.1280del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165385.1:n.1380del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165386.1:n.1447del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001203353	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 26, 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

SCV001203353

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 26, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001203353.5

#	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. ClinVar contains an entry for this variant (Variation ID: 420305). This variant has not been reported in the literature in individuals affected with CCDC78-related conditions. This variant is present in population databases (rs765483630, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln371Argfs*46) in the CCDC78 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CCDC78 cause disease.

#	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 14, 2024

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