TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23726	71401;71402;71403	chr2:178574956;178574955;178574954	chr2:179439683;179439682;179439681
N2AB	22085	66478;66479;66480	chr2:178574956;178574955;178574954	chr2:179439683;179439682;179439681
N2A	21158	63697;63698;63699	chr2:178574956;178574955;178574954	chr2:179439683;179439682;179439681
N2B	14661	44206;44207;44208	chr2:178574956;178574955;178574954	chr2:179439683;179439682;179439681
Novex-1	14786	44581;44582;44583	chr2:178574956;178574955;178574954	chr2:179439683;179439682;179439681
Novex-2	14853	44782;44783;44784	chr2:178574956;178574955;178574954	chr2:179439683;179439682;179439681
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-60
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4457
• 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/N	None	None	0.988	N	0.871	0.358	0.675418728564	gnomAD-4.0.0	1.59268E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86002E-06	0	0
I/T	None	None	0.792	N	0.632	0.156	0.515036129008	gnomAD-4.0.0	3.18536E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72004E-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	0.404	ambiguous	0.3655	ambiguous	-0.785	Destabilizing	0.717	D	0.556	neutral	None	None	None	None	I
I/C	0.6892	likely_pathogenic	0.6433	pathogenic	-0.694	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
I/D	0.8483	likely_pathogenic	0.8344	pathogenic	0.037	Stabilizing	0.991	D	0.869	deleterious	None	None	None	None	I
I/E	0.6668	likely_pathogenic	0.6519	pathogenic	-0.042	Destabilizing	0.973	D	0.874	deleterious	None	None	None	None	I
I/F	0.309	likely_benign	0.2837	benign	-0.73	Destabilizing	0.931	D	0.549	neutral	N	0.498863173	None	None	I
I/G	0.7703	likely_pathogenic	0.7427	pathogenic	-0.97	Destabilizing	0.973	D	0.85	deleterious	None	None	None	None	I
I/H	0.6018	likely_pathogenic	0.5611	ambiguous	-0.203	Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	I
I/K	0.2678	likely_benign	0.2335	benign	-0.256	Destabilizing	0.973	D	0.871	deleterious	None	None	None	None	I
I/L	0.1578	likely_benign	0.1511	benign	-0.416	Destabilizing	0.256	N	0.391	neutral	N	0.430059236	None	None	I
I/M	0.1481	likely_benign	0.1457	benign	-0.377	Destabilizing	0.964	D	0.527	neutral	N	0.480450771	None	None	I
I/N	0.3673	ambiguous	0.3587	ambiguous	-0.054	Destabilizing	0.988	D	0.871	deleterious	N	0.499036531	None	None	I
I/P	0.7911	likely_pathogenic	0.7694	pathogenic	-0.505	Destabilizing	0.991	D	0.87	deleterious	None	None	None	None	I
I/Q	0.4611	ambiguous	0.4253	ambiguous	-0.297	Destabilizing	0.991	D	0.847	deleterious	None	None	None	None	I
I/R	0.2669	likely_benign	0.2204	benign	0.281	Stabilizing	0.973	D	0.865	deleterious	None	None	None	None	I
I/S	0.3693	ambiguous	0.3424	ambiguous	-0.619	Destabilizing	0.931	D	0.692	prob.delet.	N	0.45532304	None	None	I
I/T	0.2258	likely_benign	0.2067	benign	-0.587	Destabilizing	0.792	D	0.632	neutral	N	0.427232361	None	None	I
I/V	0.0669	likely_benign	0.0663	benign	-0.505	Destabilizing	0.005	N	0.111	neutral	N	0.361084727	None	None	I
I/W	0.9307	likely_pathogenic	0.9071	pathogenic	-0.694	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	I
I/Y	0.6719	likely_pathogenic	0.6237	pathogenic	-0.436	Destabilizing	0.973	D	0.537	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.