Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002465.4(MYBPC1):c.1518C>G(p.His506Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,664 control chromosomes in the GnomAD database, including 20,958 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
MYBPC1 (HGNC:7549): (myosin binding protein C1) This gene encodes a member of the myosin-binding protein C family. Myosin-binding protein C family members are myosin-associated proteins found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The encoded protein is the slow skeletal muscle isoform of myosin-binding protein C and plays an important role in muscle contraction by recruiting muscle-type creatine kinase to myosin filaments. Mutations in this gene are associated with distal arthrogryposis type I. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0017406046).
BP6
Variant 12-101651385-C-G is Benign according to our data. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in CliVar as Benign. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
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PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Clinical Genetics, Academic Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
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Aug 15, 2013
Genetic Services Laboratory, University of Chicago
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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not providedBenign:2
Sep 04, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant is associated with the following publications: (PMID: 17000706, 23873045) -
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Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
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Arthrogryposis, distal, type 1BBenign:2
Mar 06, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -