TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16285	49078;49079;49080	chr2:178614661;178614660;178614659	chr2:179479388;179479387;179479386
N2AB	14644	44155;44156;44157	chr2:178614661;178614660;178614659	chr2:179479388;179479387;179479386
N2A	13717	41374;41375;41376	chr2:178614661;178614660;178614659	chr2:179479388;179479387;179479386
N2B	7220	21883;21884;21885	chr2:178614661;178614660;178614659	chr2:179479388;179479387;179479386
Novex-1	7345	22258;22259;22260	chr2:178614661;178614660;178614659	chr2:179479388;179479387;179479386
Novex-2	7412	22459;22460;22461	chr2:178614661;178614660;178614659	chr2:179479388;179479387;179479386
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-110
• Domain position: 24
• Structural Position: 41
• Q(SASA): 0.6497
• Predicted PPI site: I

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	rs780017546	0.183	0.946	N	0.681	0.232	0.236890367714	gnomAD-2.1.1	2.83E-05	None	None	None	None	I	None	0	0	None	5.98683E-04	0	None	0	None	0	8.94E-06	0
K/Q	rs780017546	0.183	0.946	N	0.681	0.232	0.236890367714	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	0	0	0	1.15407E-03	0	None	0	0	1.47E-05	0	0
K/Q	rs780017546	0.183	0.946	N	0.681	0.232	0.236890367714	gnomAD-4.0.0	1.11643E-05	None	None	None	None	I	None	0	0	None	4.73581E-04	0	None	0	0	3.39239E-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	0.8458	likely_pathogenic	0.8706	pathogenic	0.096	Stabilizing	0.87	D	0.633	neutral	None	None	None	None	I
K/C	0.8424	likely_pathogenic	0.8537	pathogenic	-0.23	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	I
K/D	0.966	likely_pathogenic	0.9725	pathogenic	-0.186	Destabilizing	0.959	D	0.679	prob.neutral	None	None	None	None	I
K/E	0.6955	likely_pathogenic	0.739	pathogenic	-0.195	Destabilizing	0.716	D	0.594	neutral	N	0.487810275	None	None	I
K/F	0.9137	likely_pathogenic	0.9264	pathogenic	-0.192	Destabilizing	0.994	D	0.716	prob.delet.	None	None	None	None	I
K/G	0.9299	likely_pathogenic	0.9416	pathogenic	-0.054	Destabilizing	0.959	D	0.611	neutral	None	None	None	None	I
K/H	0.502	ambiguous	0.5484	ambiguous	-0.205	Destabilizing	0.994	D	0.689	prob.neutral	None	None	None	None	I
K/I	0.5717	likely_pathogenic	0.6109	pathogenic	0.412	Stabilizing	0.973	D	0.716	prob.delet.	N	0.497690548	None	None	I
K/L	0.6333	likely_pathogenic	0.6716	pathogenic	0.412	Stabilizing	0.959	D	0.611	neutral	None	None	None	None	I
K/M	0.504	ambiguous	0.5431	ambiguous	0.052	Stabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
K/N	0.8529	likely_pathogenic	0.8826	pathogenic	0.24	Stabilizing	0.946	D	0.689	prob.neutral	N	0.490629667	None	None	I
K/P	0.9944	likely_pathogenic	0.9939	pathogenic	0.332	Stabilizing	0.979	D	0.677	prob.neutral	None	None	None	None	I
K/Q	0.3401	ambiguous	0.3889	ambiguous	0.082	Stabilizing	0.946	D	0.681	prob.neutral	N	0.50734685	None	None	I
K/R	0.1138	likely_benign	0.1177	benign	0.014	Stabilizing	0.035	N	0.376	neutral	N	0.478778735	None	None	I
K/S	0.8618	likely_pathogenic	0.8958	pathogenic	-0.134	Destabilizing	0.87	D	0.653	neutral	None	None	None	None	I
K/T	0.5782	likely_pathogenic	0.6336	pathogenic	-0.02	Destabilizing	0.946	D	0.644	neutral	N	0.509040832	None	None	I
K/V	0.5717	likely_pathogenic	0.6162	pathogenic	0.332	Stabilizing	0.959	D	0.683	prob.neutral	None	None	None	None	I
K/W	0.9219	likely_pathogenic	0.9296	pathogenic	-0.285	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	I
K/Y	0.8392	likely_pathogenic	0.8622	pathogenic	0.071	Stabilizing	0.979	D	0.716	prob.delet.	None	None	None	None	I

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.