TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5812	17659;17660;17661	chr2:178731332;178731331;178731330	chr2:179596059;179596058;179596057
N2AB	5495	16708;16709;16710	chr2:178731332;178731331;178731330	chr2:179596059;179596058;179596057
N2A	4568	13927;13928;13929	chr2:178731332;178731331;178731330	chr2:179596059;179596058;179596057
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-41
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.6706
• 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
R/T	rs1461562735	0.03	0.064	N	0.273	0.243	0.364730456448	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/T	rs1461562735	0.03	0.064	N	0.273	0.243	0.364730456448	gnomAD-4.0.0	2.73691E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63768E-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
R/A	0.4729	ambiguous	0.3975	ambiguous	-0.585	Destabilizing	0.38	N	0.333	neutral	None	None	None	None	N
R/C	0.2731	likely_benign	0.2471	benign	-0.587	Destabilizing	0.998	D	0.427	neutral	None	None	None	None	N
R/D	0.6802	likely_pathogenic	0.5975	pathogenic	-0.038	Destabilizing	0.584	D	0.47	neutral	None	None	None	None	N
R/E	0.3566	ambiguous	0.3004	benign	0.117	Stabilizing	0.037	N	0.231	neutral	None	None	None	None	N
R/F	0.5708	likely_pathogenic	0.4993	ambiguous	-0.245	Destabilizing	0.993	D	0.441	neutral	None	None	None	None	N
R/G	0.3387	likely_benign	0.2912	benign	-0.923	Destabilizing	0.679	D	0.44	neutral	N	0.488997693	None	None	N
R/H	0.1112	likely_benign	0.103	benign	-1.282	Destabilizing	0.993	D	0.528	neutral	None	None	None	None	N
R/I	0.2811	likely_benign	0.2293	benign	0.329	Stabilizing	0.947	D	0.503	neutral	N	0.504006074	None	None	N
R/K	0.101	likely_benign	0.0946	benign	-0.587	Destabilizing	0.028	N	0.227	neutral	N	0.445899133	None	None	N
R/L	0.2859	likely_benign	0.2421	benign	0.329	Stabilizing	0.737	D	0.468	neutral	None	None	None	None	N
R/M	0.2995	likely_benign	0.2476	benign	-0.207	Destabilizing	0.993	D	0.478	neutral	None	None	None	None	N
R/N	0.536	ambiguous	0.4413	ambiguous	-0.285	Destabilizing	0.872	D	0.484	neutral	None	None	None	None	N
R/P	0.8569	likely_pathogenic	0.831	pathogenic	0.046	Stabilizing	0.932	D	0.523	neutral	None	None	None	None	N
R/Q	0.1124	likely_benign	0.105	benign	-0.296	Destabilizing	0.872	D	0.5	neutral	None	None	None	None	N
R/S	0.447	ambiguous	0.3685	ambiguous	-0.924	Destabilizing	0.077	N	0.307	neutral	N	0.449054081	None	None	N
R/T	0.2158	likely_benign	0.1669	benign	-0.571	Destabilizing	0.064	N	0.273	neutral	N	0.440221167	None	None	N
R/V	0.3603	ambiguous	0.3047	benign	0.046	Stabilizing	0.872	D	0.511	neutral	None	None	None	None	N
R/W	0.2338	likely_benign	0.2151	benign	0.031	Stabilizing	0.998	D	0.45	neutral	None	None	None	None	N
R/Y	0.3967	ambiguous	0.3369	benign	0.311	Stabilizing	0.993	D	0.463	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.