NM_000070.3(CAPN3):c.1678A>G (p.Thr560Ala) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 13, 2023
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:: RCV003230470.1

Allele description [Variation Report for NM_000070.3(CAPN3):c.1678A>G (p.Thr560Ala)]

NM_000070.3(CAPN3):c.1678A>G (p.Thr560Ala)

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.1678A>G (p.Thr560Ala)

HGVS:

NC_000015.10:g.42402935A>G
NG_008660.1:g.59833A>G
NM_000070.2:c.1678A>G
NM_000070.3:c.1678A>GMANE SELECT
NM_024344.2:c.1678A>G
NM_173087.2:c.1534A>G
NM_173088.2:c.142A>G
NP_000061.1:p.Thr560Ala
NP_077320.1:p.Thr560Ala
NP_775110.1:p.Thr512Ala
NP_775111.1:p.Thr48Ala
LRG_849t1:c.1678A>G
LRG_849:g.59833A>G
LRG_849p1:p.Thr560Ala
NC_000015.9:g.42695133A>G
NM_000070.3:c.1678A>G

Protein change:

T48A

Links:

dbSNP: rs146845466

NCBI 1000 Genomes Browser:

rs146845466

Molecular consequence:

NM_000070.3:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.1534A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173088.2:c.142A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Alg14 [Vespula pensylvanica]
Alg14 [Vespula pensylvanica]
Gene ID:122636953

Gene
HPODL_01489 [Ogataea parapolymorpha DL-1]
HPODL_01489 [Ogataea parapolymorpha DL-1]
Gene ID:25770950

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003928549	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30564623, 29970176, 31862442 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003928549

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 13, 2023)

germline

clinical testing

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

Citation Link

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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

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.

Nallamilli BRR, Chakravorty S, Kesari A, Tanner A, Ankala A, Schneider T, da Silva C, Beadling R, Alexander JJ, Askree SH, Whitt Z, Bean L, Collins C, Khadilkar S, Gaitonde P, Dastur R, Wicklund M, Mozaffar T, Harms M, Rufibach L, Mittal P, Hegde M.

Ann Clin Transl Neurol. 2018 Dec;5(12):1574-1587. doi: 10.1002/acn3.649.

PubMed [citation]

PMID:: 30564623
PMCID:: PMC6292381

Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients.

Fichna JP, Macias A, Piechota M, Korostyński M, Potulska-Chromik A, Redowicz MJ, Zekanowski C.

Hum Genomics. 2018 Jul 3;12(1):34. doi: 10.1186/s40246-018-0167-1.

PubMed [citation]

PMID:: 29970176
PMCID:: PMC6029161

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003928549.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: CAPN3 c.1678A>G (p.Thr560Ala) results in a non-conservative amino acid change located in the Peptidase C2, calpain, large subunit, domain III (IPR022682) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251408 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1678A>G has been reported in the literature in at least one compound heterozygous individual affected with Limb-Girdle Muscular Dystrophy (e.g. Fichna_2018). The variant was also found in other heterozygous individuals with suspected/confirmed diagnosis of Limb-Girdle Muscular Dystrophy (e.g. Nallamilli_2018, Meinke_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all have classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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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