TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1110	3553;3554;3555	chr2:178782264;178782263;178782262	chr2:179646991;179646990;179646989
N2AB	1110	3553;3554;3555	chr2:178782264;178782263;178782262	chr2:179646991;179646990;179646989
N2A	1110	3553;3554;3555	chr2:178782264;178782263;178782262	chr2:179646991;179646990;179646989
N2B	1064	3415;3416;3417	chr2:178782264;178782263;178782262	chr2:179646991;179646990;179646989
Novex-1	1064	3415;3416;3417	chr2:178782264;178782263;178782262	chr2:179646991;179646990;179646989
Novex-2	1064	3415;3416;3417	chr2:178782264;178782263;178782262	chr2:179646991;179646990;179646989
Novex-3	1110	3553;3554;3555	chr2:178782264;178782263;178782262	chr2:179646991;179646990;179646989

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-4
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.4426
• 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/Q	None	None	0.125	N	0.264	0.17	0.190952846119	gnomAD-4.0.0	1.5905E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85654E-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	0.5393	ambiguous	0.491	ambiguous	-0.311	Destabilizing	0.754	D	0.663	neutral	None	None	None	None	N
K/C	0.9047	likely_pathogenic	0.8956	pathogenic	-0.248	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
K/D	0.9215	likely_pathogenic	0.8976	pathogenic	0.193	Stabilizing	0.956	D	0.643	neutral	None	None	None	None	N
K/E	0.5247	ambiguous	0.4534	ambiguous	0.269	Stabilizing	0.698	D	0.629	neutral	N	0.499866909	None	None	N
K/F	0.9211	likely_pathogenic	0.9005	pathogenic	-0.158	Destabilizing	0.993	D	0.729	prob.delet.	None	None	None	None	N
K/G	0.8253	likely_pathogenic	0.798	pathogenic	-0.625	Destabilizing	0.86	D	0.648	neutral	None	None	None	None	N
K/H	0.647	likely_pathogenic	0.6117	pathogenic	-0.984	Destabilizing	0.994	D	0.657	neutral	None	None	None	None	N
K/I	0.5134	ambiguous	0.4668	ambiguous	0.476	Stabilizing	0.978	D	0.733	prob.delet.	None	None	None	None	N
K/L	0.5126	ambiguous	0.4817	ambiguous	0.476	Stabilizing	0.86	D	0.648	neutral	None	None	None	None	N
K/M	0.4287	ambiguous	0.4058	ambiguous	0.264	Stabilizing	0.992	D	0.656	neutral	N	0.514204684	None	None	N
K/N	0.8208	likely_pathogenic	0.7821	pathogenic	-0.017	Destabilizing	0.942	D	0.602	neutral	D	0.530337194	None	None	N
K/P	0.6831	likely_pathogenic	0.6801	pathogenic	0.244	Stabilizing	0.978	D	0.679	prob.neutral	None	None	None	None	N
K/Q	0.2713	likely_benign	0.2422	benign	-0.085	Destabilizing	0.125	N	0.264	neutral	N	0.505132299	None	None	N
K/R	0.1079	likely_benign	0.1062	benign	-0.378	Destabilizing	0.014	N	0.189	neutral	N	0.489949363	None	None	N
K/S	0.7289	likely_pathogenic	0.6806	pathogenic	-0.61	Destabilizing	0.754	D	0.636	neutral	None	None	None	None	N
K/T	0.45	ambiguous	0.3998	ambiguous	-0.342	Destabilizing	0.942	D	0.649	neutral	N	0.495287295	None	None	N
K/V	0.4557	ambiguous	0.4168	ambiguous	0.244	Stabilizing	0.956	D	0.679	prob.neutral	None	None	None	None	N
K/W	0.9424	likely_pathogenic	0.9306	pathogenic	-0.097	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
K/Y	0.855	likely_pathogenic	0.83	pathogenic	0.202	Stabilizing	0.978	D	0.729	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.