TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24842	74749;74750;74751	chr2:178571608;178571607;178571606	chr2:179436335;179436334;179436333
N2AB	23201	69826;69827;69828	chr2:178571608;178571607;178571606	chr2:179436335;179436334;179436333
N2A	22274	67045;67046;67047	chr2:178571608;178571607;178571606	chr2:179436335;179436334;179436333
N2B	15777	47554;47555;47556	chr2:178571608;178571607;178571606	chr2:179436335;179436334;179436333
Novex-1	15902	47929;47930;47931	chr2:178571608;178571607;178571606	chr2:179436335;179436334;179436333
Novex-2	15969	48130;48131;48132	chr2:178571608;178571607;178571606	chr2:179436335;179436334;179436333
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-68
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.3871
• 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
N/D	rs1708221113	None	0.822	N	0.519	0.227	0.200317383148	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
N/D	rs1708221113	None	0.822	N	0.519	0.227	0.200317383148	gnomAD-4.0.0	2.56389E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.14179E-05	0	0	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
N/A	0.4383	ambiguous	0.42	ambiguous	-0.455	Destabilizing	0.754	D	0.625	neutral	None	None	None	None	I
N/C	0.3769	ambiguous	0.3729	ambiguous	0.381	Stabilizing	0.998	D	0.753	deleterious	None	None	None	None	I
N/D	0.5334	ambiguous	0.5277	ambiguous	-0.229	Destabilizing	0.822	D	0.519	neutral	N	0.442575534	None	None	I
N/E	0.8673	likely_pathogenic	0.8591	pathogenic	-0.264	Destabilizing	0.86	D	0.512	neutral	None	None	None	None	I
N/F	0.8495	likely_pathogenic	0.8238	pathogenic	-0.796	Destabilizing	0.956	D	0.738	prob.delet.	None	None	None	None	I
N/G	0.436	ambiguous	0.4044	ambiguous	-0.639	Destabilizing	0.754	D	0.529	neutral	None	None	None	None	I
N/H	0.2388	likely_benign	0.2218	benign	-0.707	Destabilizing	0.99	D	0.56	neutral	N	0.512496979	None	None	I
N/I	0.4786	ambiguous	0.4563	ambiguous	-0.053	Destabilizing	0.032	N	0.473	neutral	N	0.433150761	None	None	I
N/K	0.7714	likely_pathogenic	0.7439	pathogenic	0.012	Stabilizing	0.822	D	0.523	neutral	N	0.454275395	None	None	I
N/L	0.4103	ambiguous	0.3765	ambiguous	-0.053	Destabilizing	0.514	D	0.622	neutral	None	None	None	None	I
N/M	0.5742	likely_pathogenic	0.5208	ambiguous	0.506	Stabilizing	0.988	D	0.719	prob.delet.	None	None	None	None	I
N/P	0.9214	likely_pathogenic	0.9168	pathogenic	-0.161	Destabilizing	0.978	D	0.72	prob.delet.	None	None	None	None	I
N/Q	0.6803	likely_pathogenic	0.6537	pathogenic	-0.521	Destabilizing	0.978	D	0.557	neutral	None	None	None	None	I
N/R	0.766	likely_pathogenic	0.7417	pathogenic	0.125	Stabilizing	0.956	D	0.545	neutral	None	None	None	None	I
N/S	0.0765	likely_benign	0.0747	benign	-0.216	Destabilizing	0.058	N	0.151	neutral	N	0.377161405	None	None	I
N/T	0.1336	likely_benign	0.125	benign	-0.11	Destabilizing	0.698	D	0.5	neutral	N	0.383257871	None	None	I
N/V	0.4702	ambiguous	0.4438	ambiguous	-0.161	Destabilizing	0.514	D	0.623	neutral	None	None	None	None	I
N/W	0.937	likely_pathogenic	0.93	pathogenic	-0.735	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	I
N/Y	0.4304	ambiguous	0.409	ambiguous	-0.489	Destabilizing	0.97	D	0.719	prob.delet.	N	0.469558359	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.