TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22379	67360;67361;67362	chr2:178580152;178580151;178580150	chr2:179444879;179444878;179444877
N2AB	20738	62437;62438;62439	chr2:178580152;178580151;178580150	chr2:179444879;179444878;179444877
N2A	19811	59656;59657;59658	chr2:178580152;178580151;178580150	chr2:179444879;179444878;179444877
N2B	13314	40165;40166;40167	chr2:178580152;178580151;178580150	chr2:179444879;179444878;179444877
Novex-1	13439	40540;40541;40542	chr2:178580152;178580151;178580150	chr2:179444879;179444878;179444877
Novex-2	13506	40741;40742;40743	chr2:178580152;178580151;178580150	chr2:179444879;179444878;179444877
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-50
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.7817
• 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
I/T	None	None	0.005	N	0.14	0.231	0.345859378078	gnomAD-4.0.0	4.79093E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29767E-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
I/A	0.2011	likely_benign	0.2027	benign	-0.541	Destabilizing	0.103	N	0.237	neutral	None	None	None	None	I
I/C	0.5835	likely_pathogenic	0.6102	pathogenic	-0.826	Destabilizing	0.965	D	0.229	neutral	None	None	None	None	I
I/D	0.46	ambiguous	0.5249	ambiguous	-0.382	Destabilizing	0.722	D	0.323	neutral	None	None	None	None	I
I/E	0.321	likely_benign	0.3636	ambiguous	-0.46	Destabilizing	0.722	D	0.341	neutral	None	None	None	None	I
I/F	0.189	likely_benign	0.2061	benign	-0.586	Destabilizing	0.326	N	0.179	neutral	N	0.5047415	None	None	I
I/G	0.4457	ambiguous	0.4617	ambiguous	-0.669	Destabilizing	0.561	D	0.311	neutral	None	None	None	None	I
I/H	0.4276	ambiguous	0.4565	ambiguous	0.08	Stabilizing	0.818	D	0.214	neutral	None	None	None	None	I
I/K	0.268	likely_benign	0.3122	benign	-0.438	Destabilizing	0.561	D	0.309	neutral	None	None	None	None	I
I/L	0.0625	likely_benign	0.06	benign	-0.317	Destabilizing	None	N	0.071	neutral	N	0.336757577	None	None	I
I/M	0.0927	likely_benign	0.0913	benign	-0.642	Destabilizing	0.772	D	0.253	neutral	N	0.480827278	None	None	I
I/N	0.1828	likely_benign	0.2108	benign	-0.35	Destabilizing	0.772	D	0.314	neutral	N	0.437671146	None	None	I
I/P	0.5217	ambiguous	0.5365	ambiguous	-0.363	Destabilizing	0.901	D	0.295	neutral	None	None	None	None	I
I/Q	0.2721	likely_benign	0.2962	benign	-0.526	Destabilizing	0.901	D	0.282	neutral	None	None	None	None	I
I/R	0.2312	likely_benign	0.2851	benign	0.069	Stabilizing	0.901	D	0.311	neutral	None	None	None	None	I
I/S	0.1842	likely_benign	0.2033	benign	-0.727	Destabilizing	0.166	N	0.253	neutral	N	0.408791034	None	None	I
I/T	0.1972	likely_benign	0.1993	benign	-0.702	Destabilizing	0.005	N	0.14	neutral	N	0.398382039	None	None	I
I/V	0.0643	likely_benign	0.064	benign	-0.363	Destabilizing	0.036	N	0.155	neutral	N	0.406502877	None	None	I
I/W	0.7849	likely_pathogenic	0.7996	pathogenic	-0.605	Destabilizing	0.972	D	0.195	neutral	None	None	None	None	I
I/Y	0.4484	ambiguous	0.4862	ambiguous	-0.379	Destabilizing	0.004	N	0.165	neutral	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.