TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18917	56974;56975;56976	chr2:178598961;178598960;178598959	chr2:179463688;179463687;179463686
N2AB	17276	52051;52052;52053	chr2:178598961;178598960;178598959	chr2:179463688;179463687;179463686
N2A	16349	49270;49271;49272	chr2:178598961;178598960;178598959	chr2:179463688;179463687;179463686
N2B	9852	29779;29780;29781	chr2:178598961;178598960;178598959	chr2:179463688;179463687;179463686
Novex-1	9977	30154;30155;30156	chr2:178598961;178598960;178598959	chr2:179463688;179463687;179463686
Novex-2	10044	30355;30356;30357	chr2:178598961;178598960;178598959	chr2:179463688;179463687;179463686
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-25
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4514
• 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
T/K	rs370348484	None	1.0	N	0.86	0.409	None	gnomAD-4.0.0	1.59383E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86066E-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
T/A	0.2104	likely_benign	0.1803	benign	-0.63	Destabilizing	0.999	D	0.555	neutral	N	0.487995463	None	None	I
T/C	0.7006	likely_pathogenic	0.6405	pathogenic	-0.381	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
T/D	0.7245	likely_pathogenic	0.6913	pathogenic	0.135	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
T/E	0.5768	likely_pathogenic	0.5533	ambiguous	0.119	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
T/F	0.5493	ambiguous	0.4975	ambiguous	-0.755	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
T/G	0.5819	likely_pathogenic	0.4643	ambiguous	-0.865	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
T/H	0.5694	likely_pathogenic	0.5203	ambiguous	-1.131	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
T/I	0.2728	likely_benign	0.3006	benign	-0.105	Destabilizing	1.0	D	0.86	deleterious	N	0.514019918	None	None	I
T/K	0.4174	ambiguous	0.4004	ambiguous	-0.58	Destabilizing	1.0	D	0.86	deleterious	N	0.470536318	None	None	I
T/L	0.1507	likely_benign	0.1457	benign	-0.105	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	I
T/M	0.1247	likely_benign	0.1222	benign	0.077	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
T/N	0.2896	likely_benign	0.2515	benign	-0.459	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
T/P	0.8091	likely_pathogenic	0.7286	pathogenic	-0.247	Destabilizing	1.0	D	0.857	deleterious	D	0.527624241	None	None	I
T/Q	0.4205	ambiguous	0.3818	ambiguous	-0.613	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
T/R	0.4202	ambiguous	0.3773	ambiguous	-0.364	Destabilizing	1.0	D	0.855	deleterious	D	0.523543479	None	None	I
T/S	0.2141	likely_benign	0.1808	benign	-0.749	Destabilizing	0.999	D	0.553	neutral	N	0.475808247	None	None	I
T/V	0.2314	likely_benign	0.2381	benign	-0.247	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
T/W	0.8656	likely_pathogenic	0.8271	pathogenic	-0.705	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
T/Y	0.6553	likely_pathogenic	0.5649	pathogenic	-0.465	Destabilizing	1.0	D	0.861	deleterious	None	None	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.