TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15905	47938;47939;47940	chr2:178617372;178617371;178617370	chr2:179482099;179482098;179482097
N2AB	14264	43015;43016;43017	chr2:178617372;178617371;178617370	chr2:179482099;179482098;179482097
N2A	13337	40234;40235;40236	chr2:178617372;178617371;178617370	chr2:179482099;179482098;179482097
N2B	6840	20743;20744;20745	chr2:178617372;178617371;178617370	chr2:179482099;179482098;179482097
Novex-1	6965	21118;21119;21120	chr2:178617372;178617371;178617370	chr2:179482099;179482098;179482097
Novex-2	7032	21319;21320;21321	chr2:178617372;178617371;178617370	chr2:179482099;179482098;179482097
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-3
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.4285
• Predicted PPI site: I

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
N/D	None	None	0.001	N	0.119	0.122	0.124217242631	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
N/A	0.1523	likely_benign	0.1634	benign	-0.347	Destabilizing	0.228	N	0.312	neutral	None	None	None	None	I
N/C	0.2588	likely_benign	0.236	benign	0.385	Stabilizing	0.983	D	0.322	neutral	None	None	None	None	I
N/D	0.1187	likely_benign	0.1169	benign	0.262	Stabilizing	0.001	N	0.119	neutral	N	0.406523451	None	None	I
N/E	0.2143	likely_benign	0.2211	benign	0.245	Stabilizing	0.061	N	0.239	neutral	None	None	None	None	I
N/F	0.4712	ambiguous	0.4796	ambiguous	-0.643	Destabilizing	0.716	D	0.349	neutral	None	None	None	None	I
N/G	0.2485	likely_benign	0.2564	benign	-0.538	Destabilizing	0.228	N	0.25	neutral	None	None	None	None	I
N/H	0.1042	likely_benign	0.0985	benign	-0.555	Destabilizing	0.001	N	0.121	neutral	N	0.454985709	None	None	I
N/I	0.1467	likely_benign	0.1447	benign	0.075	Stabilizing	0.794	D	0.369	neutral	N	0.466802546	None	None	I
N/K	0.1499	likely_benign	0.1477	benign	0.021	Stabilizing	None	N	0.095	neutral	N	0.370822991	None	None	I
N/L	0.191	likely_benign	0.1953	benign	0.075	Stabilizing	0.418	N	0.339	neutral	None	None	None	None	I
N/M	0.2696	likely_benign	0.2773	benign	0.264	Stabilizing	0.94	D	0.321	neutral	None	None	None	None	I
N/P	0.6466	likely_pathogenic	0.6396	pathogenic	-0.039	Destabilizing	0.593	D	0.353	neutral	None	None	None	None	I
N/Q	0.201	likely_benign	0.2102	benign	-0.197	Destabilizing	0.418	N	0.217	neutral	None	None	None	None	I
N/R	0.1815	likely_benign	0.1771	benign	0.01	Stabilizing	0.129	N	0.231	neutral	None	None	None	None	I
N/S	0.0794	likely_benign	0.0809	benign	-0.085	Destabilizing	0.101	N	0.253	neutral	N	0.440283569	None	None	I
N/T	0.0891	likely_benign	0.0914	benign	0.04	Stabilizing	0.183	N	0.227	neutral	N	0.42856767	None	None	I
N/V	0.1492	likely_benign	0.1472	benign	-0.039	Destabilizing	0.593	D	0.341	neutral	None	None	None	None	I
N/W	0.7108	likely_pathogenic	0.712	pathogenic	-0.656	Destabilizing	0.983	D	0.335	neutral	None	None	None	None	I
N/Y	0.1718	likely_benign	0.1635	benign	-0.4	Destabilizing	0.213	N	0.368	neutral	N	0.482259984	None	None	I

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.