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NM_000070.3(CAPN3):c.2338G>C (p.Asp780His)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 24, 2019
Accession:
VCV000195641.7
Variation ID:
195641
Description:
single nucleotide variant
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NM_000070.3(CAPN3):c.2338G>C (p.Asp780His)

Allele ID
192802
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q15.1
Genomic location
15: 42410958 (GRCh38) GRCh38 UCSC
15: 42703156 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.42410958G>C
NC_000015.9:g.42703156G>C
NM_000070.3:c.2338G>C MANE Select NP_000061.1:p.Asp780His missense
... more HGVS
Protein change
D780H, D774H, D115H, D268H, D688H
Other names
-
Canonical SPDI
NC_000015.10:42410957:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA346865
dbSNP: rs778768583
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Aug 24, 2019 RCV000176251.8
Pathogenic 3 criteria provided, multiple submitters, no conflicts Jan 15, 2018 RCV000386470.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CAPN3 - - GRCh38
GRCh37
999 1011

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Apr 17, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000612640.2
Submitted: (Aug 31, 2018)
Evidence details
Publications
PubMed (5)
Pathogenic
(Sep 02, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000227875.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (3)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Jan 15, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000329194.6
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The D780H missense variant in the CAPN3 gene has been reported previously as a founder mutation in the Agarwal Eastern Indian population in individuals with … (more)
Pathogenic
(Dec 03, 2018)
criteria provided, single submitter
Method: research
Limb-girdle muscular dystrophy, type 2A
(Autosomal recessive inheritance)
Allele origin: germline
Broad Institute Rare Disease Group, Broad Institute
Accession: SCV001164527.1
Submitted: (Oct 03, 2019)
Evidence details
Publications
PubMed (3)
Comment:
The heterozygous p.Asp780His variant in CAPN3 was identified by our study in the compound heterozygous state, with another pathogenic variant, in one individual with limb-girdle … (more)
Pathogenic
(Aug 24, 2019)
criteria provided, single submitter
Method: clinical testing
Limb-girdle muscular dystrophy, type 2A
Allele origin: germline
Invitae
Accession: SCV000766714.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces aspartic acid with histidine at codon 780 of the CAPN3 protein (p.Asp780His). The aspartic acid residue is highly conserved and there … (more)
Pathogenic
(Sep 18, 2018)
no assertion criteria provided
Method: clinical testing
Limb-girdle muscular dystrophy, type 2A
(Autosomal recessive inheritance)
Allele origin: germline
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV000844967.1
Submitted: (Nov 01, 2018)
Evidence details
Comment:
The observed variant c.2338G>C (p.Asp780His) has not been reported in 1000 Genomes and has a minor allele frequency of 0.002% in the ExAC databases. The … (more)
Likely pathogenic
(Feb 08, 2017)
no assertion criteria provided
Method: clinical testing
Limb-girdle muscular dystrophy, type 2A
Allele origin: unknown
Counsyl
Accession: SCV000789634.2
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (1)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene. Khadilkar SV Annals of Indian Academy of Neurology 2016 PMID: 27011640
Redox state and mitochondrial respiratory chain function in skeletal muscle of LGMD2A patients. Nilsson MI PloS one 2014 PMID: 25079074
Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member with calcium bound at the fifth EF-hand. Partha SK The FEBS journal 2014 PMID: 24846670
Ancestral founder mutations in calpain-3 in the Indian Agarwal community: historical, clinical, and molecular perspective. Ankala A Muscle & nerve 2013 PMID: 23666804
Limb-girdle muscular dystrophy type 2A resulting from homozygous G2338C transversion mutation in the calpain-3 gene. Peddareddygari LR Journal of clinical neuromuscular disease 2010 PMID: 21386772
Novel mutations in the calpain 3 gene in Germany. Todorova A Clinical genetics 2005 PMID: 15733273
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CAPN3 - - - -

Text-mined citations for rs778768583...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 10, 2021