TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9278	28057;28058;28059	chr2:178711998;178711997;178711996	chr2:179576725;179576724;179576723
N2AB	8961	27106;27107;27108	chr2:178711998;178711997;178711996	chr2:179576725;179576724;179576723
N2A	8034	24325;24326;24327	chr2:178711998;178711997;178711996	chr2:179576725;179576724;179576723
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-78
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2777
• 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
K/I	None	None	0.781	N	0.824	0.334	0.529210848824	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.6217	likely_pathogenic	0.7496	pathogenic	-0.933	Destabilizing	0.399	N	0.62	neutral	None	None	None	None	N
K/C	0.7214	likely_pathogenic	0.8403	pathogenic	-1.114	Destabilizing	0.982	D	0.813	deleterious	None	None	None	None	N
K/D	0.8956	likely_pathogenic	0.9387	pathogenic	-0.616	Destabilizing	0.7	D	0.782	deleterious	None	None	None	None	N
K/E	0.337	likely_benign	0.4529	ambiguous	-0.466	Destabilizing	0.201	N	0.559	neutral	N	0.44544056	None	None	N
K/F	0.8291	likely_pathogenic	0.9118	pathogenic	-0.584	Destabilizing	0.947	D	0.819	deleterious	None	None	None	None	N
K/G	0.7786	likely_pathogenic	0.8812	pathogenic	-1.321	Destabilizing	0.7	D	0.765	deleterious	None	None	None	None	N
K/H	0.3513	ambiguous	0.4453	ambiguous	-1.644	Destabilizing	0.947	D	0.779	deleterious	None	None	None	None	N
K/I	0.3099	likely_benign	0.4734	ambiguous	0.097	Stabilizing	0.781	D	0.824	deleterious	N	0.462103523	None	None	N
K/L	0.4356	ambiguous	0.5755	pathogenic	0.097	Stabilizing	0.7	D	0.765	deleterious	None	None	None	None	N
K/M	0.2991	likely_benign	0.4343	ambiguous	-0.046	Destabilizing	0.982	D	0.769	deleterious	None	None	None	None	N
K/N	0.714	likely_pathogenic	0.8092	pathogenic	-0.901	Destabilizing	0.638	D	0.677	prob.neutral	D	0.528461801	None	None	N
K/P	0.988	likely_pathogenic	0.9954	pathogenic	-0.218	Destabilizing	0.826	D	0.789	deleterious	None	None	None	None	N
K/Q	0.1889	likely_benign	0.2551	benign	-0.954	Destabilizing	0.468	N	0.673	neutral	N	0.503293998	None	None	N
K/R	0.0756	likely_benign	0.0982	benign	-0.815	Destabilizing	0.002	N	0.268	neutral	N	0.480995928	None	None	N
K/S	0.6855	likely_pathogenic	0.7975	pathogenic	-1.59	Destabilizing	0.399	N	0.613	neutral	None	None	None	None	N
K/T	0.2877	likely_benign	0.4033	ambiguous	-1.221	Destabilizing	0.638	D	0.729	prob.delet.	N	0.475358035	None	None	N
K/V	0.3127	likely_benign	0.4759	ambiguous	-0.218	Destabilizing	0.7	D	0.802	deleterious	None	None	None	None	N
K/W	0.7679	likely_pathogenic	0.8999	pathogenic	-0.446	Destabilizing	0.982	D	0.784	deleterious	None	None	None	None	N
K/Y	0.7162	likely_pathogenic	0.8313	pathogenic	-0.12	Destabilizing	0.826	D	0.819	deleterious	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.