TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21979	66160;66161;66162	chr2:178582521;178582520;178582519	chr2:179447248;179447247;179447246
N2AB	20338	61237;61238;61239	chr2:178582521;178582520;178582519	chr2:179447248;179447247;179447246
N2A	19411	58456;58457;58458	chr2:178582521;178582520;178582519	chr2:179447248;179447247;179447246
N2B	12914	38965;38966;38967	chr2:178582521;178582520;178582519	chr2:179447248;179447247;179447246
Novex-1	13039	39340;39341;39342	chr2:178582521;178582520;178582519	chr2:179447248;179447247;179447246
Novex-2	13106	39541;39542;39543	chr2:178582521;178582520;178582519	chr2:179447248;179447247;179447246
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Fn3-47
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4484
• 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
P/A	rs1360266668	-1.698	0.998	N	0.712	0.369	0.293147016451	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
P/L	rs773647071	-0.554	1.0	N	0.871	0.446	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	0	None	0	2.8093E-04	None	0	None	0	1.78E-05	0
P/L	rs773647071	-0.554	1.0	N	0.871	0.446	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	0
P/L	rs773647071	-0.554	1.0	N	0.871	0.446	None	gnomAD-4.0.0	1.05413E-05	None	None	None	None	N	None	0	1.6685E-05	None	0	6.70901E-05	None	0	1.64745E-04	9.32763E-06	0	1.60256E-05
P/Q	None	None	1.0	N	0.865	0.461	0.550589291799	gnomAD-4.0.0	1.36917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79966E-06	0	0
P/R	rs773647071	-1.048	1.0	N	0.891	0.453	0.610832418033	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
P/R	rs773647071	-1.048	1.0	N	0.891	0.453	0.610832418033	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/R	rs773647071	-1.048	1.0	N	0.891	0.453	0.610832418033	gnomAD-4.0.0	6.58042E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47124E-05	0	0
P/S	None	None	0.999	N	0.781	0.386	0.376216005999	gnomAD-4.0.0	1.59322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43386E-05	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
P/A	0.0923	likely_benign	0.0844	benign	-1.655	Destabilizing	0.998	D	0.712	prob.delet.	N	0.480792779	None	None	N
P/C	0.7254	likely_pathogenic	0.6551	pathogenic	-1.051	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/D	0.7798	likely_pathogenic	0.6986	pathogenic	-1.892	Destabilizing	0.702	D	0.355	neutral	None	None	None	None	N
P/E	0.4788	ambiguous	0.3958	ambiguous	-1.788	Destabilizing	0.994	D	0.733	prob.delet.	None	None	None	None	N
P/F	0.7909	likely_pathogenic	0.7078	pathogenic	-1.135	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/G	0.6439	likely_pathogenic	0.5278	ambiguous	-2.055	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
P/H	0.4403	ambiguous	0.3601	ambiguous	-1.588	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/I	0.4619	ambiguous	0.3707	ambiguous	-0.606	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/K	0.3786	ambiguous	0.2949	benign	-1.433	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/L	0.2153	likely_benign	0.1653	benign	-0.606	Destabilizing	1.0	D	0.871	deleterious	N	0.503990259	None	None	N
P/M	0.4196	ambiguous	0.3348	benign	-0.505	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/N	0.6642	likely_pathogenic	0.5581	ambiguous	-1.44	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
P/Q	0.2749	likely_benign	0.2258	benign	-1.476	Destabilizing	1.0	D	0.865	deleterious	N	0.489102008	None	None	N
P/R	0.3113	likely_benign	0.247	benign	-1.031	Destabilizing	1.0	D	0.891	deleterious	N	0.491557543	None	None	N
P/S	0.3121	likely_benign	0.2297	benign	-1.951	Destabilizing	0.999	D	0.781	deleterious	N	0.497887419	None	None	N
P/T	0.249	likely_benign	0.1892	benign	-1.722	Destabilizing	0.999	D	0.799	deleterious	N	0.502090928	None	None	N
P/V	0.3128	likely_benign	0.2487	benign	-0.925	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/W	0.917	likely_pathogenic	0.8762	pathogenic	-1.46	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/Y	0.7589	likely_pathogenic	0.6545	pathogenic	-1.104	Destabilizing	1.0	D	0.89	deleterious	None	None	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.