NM_000070.3(CAPN3):c.2338G>C (p.Asp780His) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jan 15, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000386470.3

Allele description [Variation Report for NM_000070.3(CAPN3):c.2338G>C (p.Asp780His)]

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

Gene:
CAPN3:calpain 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q15.1
Genomic location:
Preferred name:
NM_000070.3(CAPN3):c.2338G>C (p.Asp780His)
HGVS:
  • NC_000015.10:g.42410958G>C
  • NG_008660.1:g.67856G>C
  • NM_000070.3:c.2338G>CMANE SELECT
  • NM_024344.1:c.2320G>C
  • NM_173087.1:c.2062G>C
  • NM_173088.1:c.802G>C
  • NM_173089.1:c.343G>C
  • NM_173090.1:c.343G>C
  • NP_000061.1:p.Asp780His
  • NP_077320.1:p.Asp774His
  • NP_775110.1:p.Asp688His
  • NP_775111.1:p.Asp268His
  • NP_775112.1:p.Asp115His
  • NP_775113.1:p.Asp115His
  • LRG_849t1:c.2338G>C
  • LRG_849:g.67856G>C
  • LRG_849p1:p.Asp780His
  • NC_000015.9:g.42703156G>C
  • NM_000070.2:c.2338G>C
Protein change:
D115H
Links:
dbSNP: rs778768583
NCBI 1000 Genomes Browser:
rs778768583
Molecular consequence:
  • NM_000070.3:c.2338G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024344.1:c.2320G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173087.1:c.2062G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173088.1:c.802G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173089.1:c.343G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173090.1:c.343G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
5

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000227875EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Sep 2, 2016)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000329194GeneDxcriteria provided, single submitter
Pathogenic
(Jan 15, 2018)
germlineclinical testing

Citation Link,

SCV000612640Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Apr 17, 2017)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown5not providednot providednot providednot providedclinical testing

Citations

PubMed

Ancestral founder mutations in calpain-3 in the Indian Agarwal community: historical, clinical, and molecular perspective.

Ankala A, Kohn JN, Dastur R, Gaitonde P, Khadilkar SV, Hegde MR.

Muscle Nerve. 2013 Jun;47(6):931-7. doi: 10.1002/mus.23763. Epub 2013 May 11.

PubMed [citation]
PMID:
23666804

Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene.

Khadilkar SV, Chaudhari CR, Dastur RS, Gaitonde PS, Yadav JG.

Ann Indian Acad Neurol. 2016 Jan-Mar;19(1):108-11. doi: 10.4103/0972-2327.175435.

PubMed [citation]
PMID:
27011640
PMCID:
PMC4782525
See all PubMed Citations (6)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000227875.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided5not providednot providednot provided

From GeneDx, SCV000329194.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 LGMD2A (Ankala, et al., 2013; Todorova et al., 2005). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Additionally, missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with limb-girdle muscular dystrophy (Stenson et al., 2014). The D780H variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Therefore, we interpret D780H as a pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Athena Diagnostics Inc, SCV000612640.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

Support Center