TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5379	16360;16361;16362	chr2:178733041;178733040;178733039	chr2:179597768;179597767;179597766
N2AB	5062	15409;15410;15411	chr2:178733041;178733040;178733039	chr2:179597768;179597767;179597766
N2A	4135	12628;12629;12630	chr2:178733041;178733040;178733039	chr2:179597768;179597767;179597766
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-37
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.4292
• 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/T	rs752346935	-0.874	0.638	N	0.689	0.295	0.276065633971	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
K/T	rs752346935	-0.874	0.638	N	0.689	0.295	0.276065633971	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/T	rs752346935	-0.874	0.638	N	0.689	0.295	0.276065633971	gnomAD-4.0.0	1.67356E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.28877E-05	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	0.7518	likely_pathogenic	0.6846	pathogenic	-0.711	Destabilizing	0.399	N	0.565	neutral	None	None	None	None	N
K/C	0.8951	likely_pathogenic	0.8721	pathogenic	-0.778	Destabilizing	0.982	D	0.682	prob.neutral	None	None	None	None	N
K/D	0.9013	likely_pathogenic	0.8657	pathogenic	-0.553	Destabilizing	0.25	N	0.639	neutral	None	None	None	None	N
K/E	0.5579	ambiguous	0.4551	ambiguous	-0.434	Destabilizing	0.007	N	0.437	neutral	N	0.411981347	None	None	N
K/F	0.9472	likely_pathogenic	0.9305	pathogenic	-0.421	Destabilizing	0.947	D	0.721	prob.delet.	None	None	None	None	N
K/G	0.8389	likely_pathogenic	0.7939	pathogenic	-1.092	Destabilizing	0.399	N	0.674	neutral	None	None	None	None	N
K/H	0.463	ambiguous	0.4224	ambiguous	-1.494	Destabilizing	0.947	D	0.699	prob.neutral	None	None	None	None	N
K/I	0.7175	likely_pathogenic	0.6491	pathogenic	0.286	Stabilizing	0.781	D	0.737	prob.delet.	N	0.498909685	None	None	N
K/L	0.7313	likely_pathogenic	0.6694	pathogenic	0.286	Stabilizing	0.7	D	0.69	prob.neutral	None	None	None	None	N
K/M	0.5805	likely_pathogenic	0.5138	ambiguous	0.264	Stabilizing	0.982	D	0.691	prob.neutral	None	None	None	None	N
K/N	0.7879	likely_pathogenic	0.7268	pathogenic	-0.768	Destabilizing	0.638	D	0.617	neutral	N	0.513492348	None	None	N
K/P	0.9611	likely_pathogenic	0.9534	pathogenic	-0.016	Destabilizing	0.826	D	0.712	prob.delet.	None	None	None	None	N
K/Q	0.2607	likely_benign	0.2124	benign	-0.856	Destabilizing	0.468	N	0.614	neutral	N	0.452731891	None	None	N
K/R	0.0878	likely_benign	0.0812	benign	-0.808	Destabilizing	0.004	N	0.406	neutral	N	0.462236809	None	None	N
K/S	0.7801	likely_pathogenic	0.7142	pathogenic	-1.402	Destabilizing	0.399	N	0.517	neutral	None	None	None	None	N
K/T	0.4948	ambiguous	0.42	ambiguous	-1.075	Destabilizing	0.638	D	0.689	prob.neutral	N	0.486804393	None	None	N
K/V	0.6608	likely_pathogenic	0.5936	pathogenic	-0.016	Destabilizing	0.7	D	0.696	prob.neutral	None	None	None	None	N
K/W	0.9181	likely_pathogenic	0.894	pathogenic	-0.31	Destabilizing	0.982	D	0.653	neutral	None	None	None	None	N
K/Y	0.8641	likely_pathogenic	0.8307	pathogenic	0.006	Stabilizing	0.826	D	0.723	prob.delet.	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.