NM_001378030.1(CCDC78):c.1039C>T (p.His347Tyr) AND Congenital myopathy with internal nuclei and atypical cores

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 24, 2024
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:: RCV000550251.8

Allele description [Variation Report for NM_001378030.1(CCDC78):c.1039C>T (p.His347Tyr)]

NM_001378030.1(CCDC78):c.1039C>T (p.His347Tyr)

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.1039C>T (p.His347Tyr)

HGVS:

NC_000016.10:g.724120G>A
NG_032932.1:g.7354C>T
NM_001031737.3:c.1039C>T
NM_001378030.1:c.1039C>TMANE SELECT
NM_001378031.1:c.953+202C>T
NM_001378033.1:c.472C>T
NP_001026907.2:p.His347Tyr
NP_001364959.1:p.His347Tyr
NP_001364962.1:p.His158Tyr
LRG_705t1:c.1039C>T
LRG_705t2:c.1039C>T
LRG_705:g.7354C>T
LRG_705p1:p.His347Tyr
LRG_705p2:p.His347Tyr
NC_000016.9:g.774120G>A
NM_001031737.2:c.1039C>T
NR_165382.1:n.1596C>T
NR_165383.1:n.1242C>T
NR_165384.1:n.1207C>T
NR_165385.1:n.1307C>T
NR_165386.1:n.1374C>T

Protein change:

H158Y

Links:

dbSNP: rs369908634

NCBI 1000 Genomes Browser:

rs369908634

Molecular consequence:

NM_001378031.1:c.953+202C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001031737.3:c.1039C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378030.1:c.1039C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378033.1:c.472C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_165382.1:n.1596C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165383.1:n.1242C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165384.1:n.1207C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165385.1:n.1307C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165386.1:n.1374C>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

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txid754085[Organism:noexp] (2)
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txid550683[Organism:noexp] (104)
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txid694519[Organism:noexp] (2)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000652728	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 2024)	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

SCV000652728

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 2024)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000652728.7

#	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 histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 347 of the CCDC78 protein (p.His347Tyr). This variant is present in population databases (rs369908634, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CCDC78-related conditions. ClinVar contains an entry for this variant (Variation ID: 473246). 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 with a negative predictive value of 80%. 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.

#	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: Sep 29, 2024

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