TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14760	44503;44504;44505	chr2:178630244;178630243;178630242	chr2:179494971;179494970;179494969
N2AB	13119	39580;39581;39582	chr2:178630244;178630243;178630242	chr2:179494971;179494970;179494969
N2A	12192	36799;36800;36801	chr2:178630244;178630243;178630242	chr2:179494971;179494970;179494969
N2B	5695	17308;17309;17310	chr2:178630244;178630243;178630242	chr2:179494971;179494970;179494969
Novex-1	5820	17683;17684;17685	chr2:178630244;178630243;178630242	chr2:179494971;179494970;179494969
Novex-2	5887	17884;17885;17886	chr2:178630244;178630243;178630242	chr2:179494971;179494970;179494969
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: Ig-98
• Domain position: 86
• Structural Position: 177
• Q(SASA): 0.5082
• 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/E	None	None	0.997	N	0.679	0.332	0.242244723065	gnomAD-4.0.0	6.84556E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99795E-07	0	0
K/R	rs2059635881	None	0.997	N	0.613	0.198	0.28297238246	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	0.8117	likely_pathogenic	0.8445	pathogenic	-0.261	Destabilizing	0.998	D	0.699	prob.delet.	None	None	None	None	N
K/C	0.9228	likely_pathogenic	0.9331	pathogenic	-0.316	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/D	0.9541	likely_pathogenic	0.9612	pathogenic	-0.227	Destabilizing	0.999	D	0.724	deleterious	None	None	None	None	N
K/E	0.6216	likely_pathogenic	0.6777	pathogenic	-0.133	Destabilizing	0.997	D	0.679	prob.neutral	N	0.415141524	None	None	N
K/F	0.9128	likely_pathogenic	0.9294	pathogenic	0.073	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
K/G	0.8678	likely_pathogenic	0.8818	pathogenic	-0.6	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
K/H	0.5864	likely_pathogenic	0.6017	pathogenic	-0.905	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/I	0.5868	likely_pathogenic	0.6282	pathogenic	0.603	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
K/L	0.5894	likely_pathogenic	0.6166	pathogenic	0.603	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
K/M	0.4531	ambiguous	0.5127	ambiguous	0.247	Stabilizing	1.0	D	0.752	deleterious	N	0.508934265	None	None	N
K/N	0.8214	likely_pathogenic	0.8545	pathogenic	-0.342	Destabilizing	0.999	D	0.757	deleterious	D	0.56969792	None	None	N
K/P	0.9732	likely_pathogenic	0.9741	pathogenic	0.344	Stabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
K/Q	0.3199	likely_benign	0.3509	ambiguous	-0.351	Destabilizing	0.999	D	0.787	deleterious	N	0.412751596	None	None	N
K/R	0.1459	likely_benign	0.1445	benign	-0.614	Destabilizing	0.997	D	0.613	neutral	N	0.424369624	None	None	N
K/S	0.8419	likely_pathogenic	0.8656	pathogenic	-0.796	Destabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
K/T	0.5003	ambiguous	0.5533	ambiguous	-0.52	Destabilizing	0.999	D	0.695	prob.delet.	N	0.412094268	None	None	N
K/V	0.6423	likely_pathogenic	0.6747	pathogenic	0.344	Stabilizing	0.999	D	0.652	prob.neutral	None	None	None	None	N
K/W	0.9292	likely_pathogenic	0.9373	pathogenic	0.08	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Y	0.8447	likely_pathogenic	0.8585	pathogenic	0.345	Stabilizing	1.0	D	0.742	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.