| Gene/Disease Pair: | PLN : Intrinsic Cardiomyopathy |
| MONDO:0000591 | ORPHA:167848 | OMIM:115196 | |
| Mode of Inheritance: | Autosomal dominant inheritance (HP:0000006) |
| SOP: | Gene Clinical Validity Standard Operating Procedures (SOP), Version 5 |
|
Genetic Evidence
|
Case-Level Data
|
Evidence Type | Case Information Type | Guidelines | Scores | PMIDs/Notes | ||||||
| Default | Range | Max | Points | Tally | ||||||||
|
Variant Evidence
|
Autosomal Dominant or X-linked Disorder | Variant is de novo | 2 | 0-3 | 12 |
0.00
|
0 | |||||
| Proband with predicted or proven null variant | 1.5 | 0-2 | 10 | 0.00 | 0 | |||||||
| Proband with other variant type with some evidence of gene impact | 0.5 | 0-1.5 | 7 |
7.00
|
7 |
Minamisawa S et al. 2003 Apr 25 (PMID:12705874); Haghighi K et al. 2003 Mar (PMID:12639993); Chiu C et al. 2007 Sep (PMID:17655857); Landstrom AP et al. 2011 Jan (PMID:21167350); DeWitt MM et al. 2006 Oct 3 (PMID:17010801); van der Zwaag PA et al. 2012 Nov (PMID:22820313); Schmitt JP et al. 2003 Feb 28 (PMID:12610310); Medeiros A et al. 2011 Dec (PMID:22137083);
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| Autosomal Recessive Disease | Two variants in trans and at least one de novo or a predicted/proven null variant | 2 | 0-3 | 12 |
|
Haghighi K et al. 2003 Mar (PMID:12639993);
|
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| Two variants (not predicted/proven null) with some evidence of gene impact in trans | 1 | 0-1.5 |
0.50
|
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| Segregation Evidence | Evidence of segregation in one or more families | Sequencing Method | 0-3 | 3 |
1.50
|
1.5 | ||||||
| Total LOD Score | Canditate Gene Sequencing | Exome/Genome or all genes sequenced in linkage region | ||||||||||
| 2-2.99 | 0.5 | 1 |
Haghighi K et al. 2003 Mar (PMID:12639993);
|
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| 3-4.99 | 1 | 2 |
Haghighi K et al. 2006 Jan 31 (PMID:16432188);
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| ≥5 | 1.5 | 3 |
Schmitt JP et al. 2003 Feb 28 (PMID:12610310);
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|
Case-Control Data
|
Case-Control Study Type | Case-Control Quality Criteria | Guidelines | Scores | PMIDs/Notes | |||||||
| Points/Study | Max | Points | Tally | |||||||||
| Single Variant Analysis | 1. Variant Detection Methodology 2. Power 3. Bias and confounding 4. Statistical Significance |
0-6 | 12 |
|
||||||||
| Aggregate Variant Analysis | 0-6 |
1.50
|
Walsh R et al. 2017 Feb (PMID:27532257);
|
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| Total Genetic Evidence Points (Maximum 12) | 10.5 |
|
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|
Experimental Evidence
|
Evidence Category | Evidence Type | Guidelines | Scores | PMIDs/Notes | |||||||
| Default | Range | Max | Points | Tally | ||||||||
| Function | Biochemical Function | 0.5 | 0 - 2 | 2 |
0.50
|
2 |
Toyofuku T et al. 1993 Feb 5 (PMID:8428955);
|
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| Protein Interaction | 0.5 | 0 - 2 | ||||||||||
| Expression | 0.5 | 0 - 2 | 1.50 |
McTiernan CF et al. 1999 Mar (PMID:10198197); Meyer M et al. 1995 Aug 15 (PMID:7641356);
|
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| Functional Alteration | Patient cells | 1 | 0 - 2 | 2 |
|
0.5 | ||||||
| Non-patient cells | 0.5 | 0 - 1 | 0.50 |
Haghighi K et al. 2003 Mar (PMID:12639993);
|
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| Models | Non-human model organism | 2 | 0 - 4 | 4 | 5.00 | 4 |
Dash R et al. 2001 Feb 13 (PMID:11171800); Kadambi VJ et al. 1996 Jan 15 (PMID:8567978); Luo W et al. 1994 Sep (PMID:8062415); Luo W et al. 1998 Feb 20 (PMID:9468536); Pattison JS et al. 2008 Apr (PMID:17882530); Haghighi K et al. 2006 Jan 31 (PMID:16432188); Haghighi K et al. 2006 Jan 31 (PMID:16432188); (Only two non-human model organism were awarded points PMIDs: 16432188 and 11171800. The others did not obtain a score due to insufficient evidence or phenotyping.)
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| Cell culture model | 1 | 0 - 2 | ||||||||||
| Rescue | Rescue in human | 2 | 0 - 4 |
|
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| Rescue in non-human model organism | 2 | 0 - 4 | ||||||||||
| Rescue in cell culture model | 1 | 0 - 2 | ||||||||||
| Rescue in patient cells | 1 | 0 - 2 | ||||||||||
| Total Experimental Evidence Points (Maximum 6) | 6 |
|
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| Assertion criteria | Genetic Evidence (0-12 points) | Experimental Evidence
(0-6 points) |
Total Points
(0-18) |
Replication Over Time (Y/N) | ||
| Description | Case-level, family segregation, or case-control data that support the gene-disease association | Gene-level experimental evidence that support the gene-disease association | Sum of Genetic & Experimental
Evidence |
> 2 pubs w/ convincing evidence over time (>3 yrs) | ||
| Assigned Points | 10.5 | 6 | 16.5 | YES | ||
| CALCULATED CLASSIFICATION | LIMITED | 1-6 | ||||
| MODERATE | 7-11 | |||||
| STRONG | 12-18 | |||||
| DEFINITIVE | 12-18 AND replication over time | |||||
| Valid contradictory evidence (Y/N)*
|
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| CALCULATED CLASSIFICATION (DATE) |
DEFINITIVE
08/29/2017
|
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| EXPERT CURATION (DATE) |
DEFINITIVE
09/19/2017
Approved by the Hypertrophic cardiomyopathy Gene Curation Expert Panel
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