TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19617	59074;59075;59076	chr2:178593359;178593358;178593357	chr2:179458086;179458085;179458084
N2AB	17976	54151;54152;54153	chr2:178593359;178593358;178593357	chr2:179458086;179458085;179458084
N2A	17049	51370;51371;51372	chr2:178593359;178593358;178593357	chr2:179458086;179458085;179458084
N2B	10552	31879;31880;31881	chr2:178593359;178593358;178593357	chr2:179458086;179458085;179458084
Novex-1	10677	32254;32255;32256	chr2:178593359;178593358;178593357	chr2:179458086;179458085;179458084
Novex-2	10744	32455;32456;32457	chr2:178593359;178593358;178593357	chr2:179458086;179458085;179458084
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-30
• Domain position: 39
• Structural Position: 42
• Q(SASA): 0.2394
• 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/M	rs777196126	-0.402	1.0	N	0.789	0.412	0.365317461125	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
K/M	rs777196126	-0.402	1.0	N	0.789	0.412	0.365317461125	gnomAD-4.0.0	4.77626E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.2996E-05	0
K/R	rs777196126	None	0.217	N	0.363	0.118	0.318252033908	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07297E-04	0
K/R	rs777196126	None	0.217	N	0.363	0.118	0.318252033908	gnomAD-4.0.0	6.40897E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.70259E-05	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	0.9713	likely_pathogenic	0.9649	pathogenic	-1.374	Destabilizing	0.996	D	0.7	prob.neutral	None	None	None	None	N
K/C	0.9313	likely_pathogenic	0.9178	pathogenic	-1.354	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/D	0.996	likely_pathogenic	0.9957	pathogenic	-2.246	Highly Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
K/E	0.9341	likely_pathogenic	0.9153	pathogenic	-1.915	Destabilizing	0.989	D	0.728	prob.delet.	N	0.489980019	None	None	N
K/F	0.9794	likely_pathogenic	0.9711	pathogenic	-0.722	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/G	0.9788	likely_pathogenic	0.9755	pathogenic	-1.85	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
K/H	0.8277	likely_pathogenic	0.7936	pathogenic	-1.408	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/I	0.9207	likely_pathogenic	0.8927	pathogenic	-0.001	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/L	0.8768	likely_pathogenic	0.8343	pathogenic	-0.001	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
K/M	0.7182	likely_pathogenic	0.6532	pathogenic	-0.406	Destabilizing	1.0	D	0.789	deleterious	N	0.521289821	None	None	N
K/N	0.9852	likely_pathogenic	0.9819	pathogenic	-1.892	Destabilizing	0.998	D	0.785	deleterious	N	0.512857214	None	None	N
K/P	0.9991	likely_pathogenic	0.9989	pathogenic	-0.443	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/Q	0.6216	likely_pathogenic	0.5584	ambiguous	-1.474	Destabilizing	0.997	D	0.79	deleterious	N	0.469407002	None	None	N
K/R	0.1394	likely_benign	0.1248	benign	-0.627	Destabilizing	0.217	N	0.363	neutral	N	0.456123621	None	None	N
K/S	0.9824	likely_pathogenic	0.9769	pathogenic	-2.345	Highly Destabilizing	0.996	D	0.743	deleterious	None	None	None	None	N
K/T	0.9241	likely_pathogenic	0.9085	pathogenic	-1.752	Destabilizing	0.998	D	0.776	deleterious	N	0.477356266	None	None	N
K/V	0.8902	likely_pathogenic	0.8547	pathogenic	-0.443	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
K/W	0.9673	likely_pathogenic	0.9554	pathogenic	-0.786	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/Y	0.9134	likely_pathogenic	0.8855	pathogenic	-0.435	Destabilizing	1.0	D	0.827	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.