NM_001378030.1(CCDC78):c.1043G>T (p.Arg348Leu) AND Congenital myopathy with internal nuclei and atypical cores

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 4, 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:: RCV001297422.7

Allele description [Variation Report for NM_001378030.1(CCDC78):c.1043G>T (p.Arg348Leu)]

NM_001378030.1(CCDC78):c.1043G>T (p.Arg348Leu)

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.1043G>T (p.Arg348Leu)

HGVS:

NC_000016.10:g.724116C>A
NG_032932.1:g.7358G>T
NM_001031737.3:c.1043G>T
NM_001378030.1:c.1043G>TMANE SELECT
NM_001378031.1:c.953+206G>T
NM_001378033.1:c.476G>T
NP_001026907.2:p.Arg348Leu
NP_001364959.1:p.Arg348Leu
NP_001364962.1:p.Arg159Leu
LRG_705t1:c.1043G>T
LRG_705t2:c.1043G>T
LRG_705:g.7358G>T
LRG_705p1:p.Arg348Leu
LRG_705p2:p.Arg348Leu
NC_000016.9:g.774116C>A
NR_165382.1:n.1600G>T
NR_165383.1:n.1246G>T
NR_165384.1:n.1211G>T
NR_165385.1:n.1311G>T
NR_165386.1:n.1378G>T

Protein change:

R159L

Links:

dbSNP: rs142170929

NCBI 1000 Genomes Browser:

rs142170929

Molecular consequence:

NM_001378031.1:c.953+206G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001031737.3:c.1043G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378030.1:c.1043G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378033.1:c.476G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_165382.1:n.1600G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165383.1:n.1246G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165384.1:n.1211G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165385.1:n.1311G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165386.1:n.1378G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001486434	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 4, 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

SCV001486434

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 4, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001486434.4

#	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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CCDC78-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 348 of the CCDC78 protein (p.Arg348Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine.

#	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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