TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8400	25423;25424;25425	chr2:178717676;178717675;178717674	chr2:179582403;179582402;179582401
N2AB	8083	24472;24473;24474	chr2:178717676;178717675;178717674	chr2:179582403;179582402;179582401
N2A	7156	21691;21692;21693	chr2:178717676;178717675;178717674	chr2:179582403;179582402;179582401
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-69
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2214
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
L/W	None	None	0.999	D	0.718	0.612	0.888760345717	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
L/A	0.8059	likely_pathogenic	0.8134	pathogenic	-1.872	Destabilizing	0.951	D	0.488	neutral	None	None	None	None	N
L/C	0.8688	likely_pathogenic	0.8649	pathogenic	-0.982	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
L/D	0.9917	likely_pathogenic	0.9935	pathogenic	-1.862	Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	N
L/E	0.9137	likely_pathogenic	0.9328	pathogenic	-1.642	Destabilizing	0.99	D	0.792	deleterious	None	None	None	None	N
L/F	0.4467	ambiguous	0.4609	ambiguous	-1.117	Destabilizing	0.953	D	0.586	neutral	D	0.525799903	None	None	N
L/G	0.9579	likely_pathogenic	0.964	pathogenic	-2.358	Highly Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
L/H	0.8325	likely_pathogenic	0.8527	pathogenic	-1.644	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
L/I	0.1142	likely_benign	0.1064	benign	-0.483	Destabilizing	0.002	N	0.296	neutral	None	None	None	None	N
L/K	0.8589	likely_pathogenic	0.8952	pathogenic	-1.246	Destabilizing	0.802	D	0.735	prob.delet.	None	None	None	None	N
L/M	0.2455	likely_benign	0.2364	benign	-0.388	Destabilizing	0.86	D	0.611	neutral	N	0.508429664	None	None	N
L/N	0.9559	likely_pathogenic	0.9602	pathogenic	-1.642	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
L/P	0.9427	likely_pathogenic	0.9442	pathogenic	-0.926	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
L/Q	0.6633	likely_pathogenic	0.7134	pathogenic	-1.483	Destabilizing	0.994	D	0.759	deleterious	None	None	None	None	N
L/R	0.7545	likely_pathogenic	0.8143	pathogenic	-1.082	Destabilizing	0.982	D	0.761	deleterious	None	None	None	None	N
L/S	0.9243	likely_pathogenic	0.9295	pathogenic	-2.3	Highly Destabilizing	0.99	D	0.727	prob.delet.	D	0.555513953	None	None	N
L/T	0.8419	likely_pathogenic	0.8369	pathogenic	-1.929	Destabilizing	0.953	D	0.628	neutral	None	None	None	None	N
L/V	0.1581	likely_benign	0.1495	benign	-0.926	Destabilizing	0.008	N	0.376	neutral	N	0.504665008	None	None	N
L/W	0.6956	likely_pathogenic	0.7317	pathogenic	-1.42	Destabilizing	0.999	D	0.718	prob.delet.	D	0.530029866	None	None	N
L/Y	0.8365	likely_pathogenic	0.8578	pathogenic	-1.058	Destabilizing	0.866	D	0.697	prob.neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.