TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14150	42673;42674;42675	chr2:178634051;178634050;178634049	chr2:179498778;179498777;179498776
N2AB	12509	37750;37751;37752	chr2:178634051;178634050;178634049	chr2:179498778;179498777;179498776
N2A	11582	34969;34970;34971	chr2:178634051;178634050;178634049	chr2:179498778;179498777;179498776
N2B	5085	15478;15479;15480	chr2:178634051;178634050;178634049	chr2:179498778;179498777;179498776
Novex-1	5210	15853;15854;15855	chr2:178634051;178634050;178634049	chr2:179498778;179498777;179498776
Novex-2	5277	16054;16055;16056	chr2:178634051;178634050;178634049	chr2:179498778;179498777;179498776
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-92
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4322
• 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
D/N	rs1184338421	-0.188	1.0	N	0.693	0.348	0.330331372229	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
D/N	rs1184338421	-0.188	1.0	N	0.693	0.348	0.330331372229	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	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
D/A	0.5614	ambiguous	0.5312	ambiguous	-0.359	Destabilizing	1.0	D	0.816	deleterious	N	0.515486611	None	None	N
D/C	0.9472	likely_pathogenic	0.935	pathogenic	-0.098	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/E	0.5359	ambiguous	0.5008	ambiguous	-0.392	Destabilizing	1.0	D	0.477	neutral	D	0.64059904	None	None	N
D/F	0.9537	likely_pathogenic	0.9455	pathogenic	-0.147	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/G	0.4808	ambiguous	0.4322	ambiguous	-0.61	Destabilizing	1.0	D	0.8	deleterious	D	0.602299001	None	None	N
D/H	0.7515	likely_pathogenic	0.7484	pathogenic	-0.162	Destabilizing	1.0	D	0.791	deleterious	D	0.58376843	None	None	N
D/I	0.8853	likely_pathogenic	0.8694	pathogenic	0.269	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/K	0.845	likely_pathogenic	0.847	pathogenic	0.044	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
D/L	0.8924	likely_pathogenic	0.8753	pathogenic	0.269	Stabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
D/M	0.9504	likely_pathogenic	0.9397	pathogenic	0.421	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
D/N	0.1492	likely_benign	0.1574	benign	-0.258	Destabilizing	1.0	D	0.693	prob.neutral	N	0.467930235	None	None	N
D/P	0.7704	likely_pathogenic	0.8015	pathogenic	0.084	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
D/Q	0.8499	likely_pathogenic	0.8467	pathogenic	-0.199	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/R	0.9057	likely_pathogenic	0.9018	pathogenic	0.251	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
D/S	0.3291	likely_benign	0.3066	benign	-0.414	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
D/T	0.6993	likely_pathogenic	0.665	pathogenic	-0.22	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
D/V	0.7762	likely_pathogenic	0.7355	pathogenic	0.084	Stabilizing	1.0	D	0.857	deleterious	D	0.642804253	None	None	N
D/W	0.9911	likely_pathogenic	0.9887	pathogenic	0.016	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
D/Y	0.6962	likely_pathogenic	0.6717	pathogenic	0.091	Stabilizing	1.0	D	0.835	deleterious	D	0.58376843	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.