TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23175	69748;69749;69750	chr2:178576721;178576720;178576719	chr2:179441448;179441447;179441446
N2AB	21534	64825;64826;64827	chr2:178576721;178576720;178576719	chr2:179441448;179441447;179441446
N2A	20607	62044;62045;62046	chr2:178576721;178576720;178576719	chr2:179441448;179441447;179441446
N2B	14110	42553;42554;42555	chr2:178576721;178576720;178576719	chr2:179441448;179441447;179441446
Novex-1	14235	42928;42929;42930	chr2:178576721;178576720;178576719	chr2:179441448;179441447;179441446
Novex-2	14302	43129;43130;43131	chr2:178576721;178576720;178576719	chr2:179441448;179441447;179441446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-56
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2738
• 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
H/N	None	None	0.491	N	0.562	0.061	0.219573609325	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85922E-06	0	0
H/P	None	None	0.873	N	0.689	0.294	0.343101102393	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79946E-06	0	0
H/R	rs1186507360	-1.87	0.662	N	0.599	0.174	0.234412748748	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
H/R	rs1186507360	-1.87	0.662	N	0.599	0.174	0.234412748748	gnomAD-4.0.0	1.36873E-06	None	None	None	None	N	None	2.99025E-05	0	None	0	0	None	0	0	0	0	1.65706E-05

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
H/A	0.4831	ambiguous	0.4936	ambiguous	-1.359	Destabilizing	0.103	N	0.581	neutral	None	None	None	None	N
H/C	0.1582	likely_benign	0.172	benign	-0.698	Destabilizing	0.002	N	0.561	neutral	None	None	None	None	N
H/D	0.6481	likely_pathogenic	0.7052	pathogenic	-1.15	Destabilizing	0.491	N	0.648	neutral	N	0.459219854	None	None	N
H/E	0.6113	likely_pathogenic	0.6484	pathogenic	-1.018	Destabilizing	0.561	D	0.537	neutral	None	None	None	None	N
H/F	0.167	likely_benign	0.1659	benign	0.128	Stabilizing	0.39	N	0.646	neutral	None	None	None	None	N
H/G	0.6993	likely_pathogenic	0.7298	pathogenic	-1.719	Destabilizing	0.345	N	0.61	neutral	None	None	None	None	N
H/I	0.1788	likely_benign	0.1669	benign	-0.333	Destabilizing	0.002	N	0.566	neutral	None	None	None	None	N
H/K	0.5219	ambiguous	0.5633	ambiguous	-1.186	Destabilizing	0.561	D	0.637	neutral	None	None	None	None	N
H/L	0.1223	likely_benign	0.1261	benign	-0.333	Destabilizing	0.029	N	0.609	neutral	N	0.398075395	None	None	N
H/M	0.4194	ambiguous	0.3973	ambiguous	-0.562	Destabilizing	0.818	D	0.679	prob.neutral	None	None	None	None	N
H/N	0.2113	likely_benign	0.2299	benign	-1.339	Destabilizing	0.491	N	0.562	neutral	N	0.43732443	None	None	N
H/P	0.915	likely_pathogenic	0.9368	pathogenic	-0.66	Destabilizing	0.873	D	0.689	prob.neutral	N	0.468393043	None	None	N
H/Q	0.3154	likely_benign	0.3315	benign	-1.011	Destabilizing	0.662	D	0.621	neutral	N	0.443519683	None	None	N
H/R	0.2243	likely_benign	0.2582	benign	-1.511	Destabilizing	0.662	D	0.599	neutral	N	0.434225409	None	None	N
H/S	0.3822	ambiguous	0.3993	ambiguous	-1.433	Destabilizing	0.021	N	0.402	neutral	None	None	None	None	N
H/T	0.3714	ambiguous	0.3698	ambiguous	-1.206	Destabilizing	0.209	N	0.611	neutral	None	None	None	None	N
H/V	0.18	likely_benign	0.1751	benign	-0.66	Destabilizing	0.083	N	0.619	neutral	None	None	None	None	N
H/W	0.2554	likely_benign	0.2648	benign	0.467	Stabilizing	0.972	D	0.685	prob.neutral	None	None	None	None	N
H/Y	0.069	likely_benign	0.0711	benign	0.474	Stabilizing	0.003	N	0.27	neutral	N	0.432612043	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.