TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8308	25147;25148;25149	chr2:178718084;178718083;178718082	chr2:179582811;179582810;179582809
N2AB	7991	24196;24197;24198	chr2:178718084;178718083;178718082	chr2:179582811;179582810;179582809
N2A	7064	21415;21416;21417	chr2:178718084;178718083;178718082	chr2:179582811;179582810;179582809
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-68
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.8927
• 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/S	rs373770383	0.067	0.116	N	0.319	0.177	None	gnomAD-2.1.1	4.64E-05	None	None	None	None	N	None	5.37279E-04	0	None	0	0	None	0	None	0	0	0
P/S	rs373770383	0.067	0.116	N	0.319	0.177	None	gnomAD-3.1.2	1.38053E-04	None	None	None	None	N	None	4.82695E-04	0	0	0	0	None	0	0	0	0	4.78927E-04
P/S	rs373770383	0.067	0.116	N	0.319	0.177	None	gnomAD-4.0.0	2.23131E-05	None	None	None	None	N	None	4.53999E-04	0	None	0	0	None	0	0	0	0	3.20277E-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
P/A	0.1064	likely_benign	0.1518	benign	-0.303	Destabilizing	0.001	N	0.15	neutral	N	0.470218787	None	None	N
P/C	0.8284	likely_pathogenic	0.9014	pathogenic	-0.733	Destabilizing	0.952	D	0.303	neutral	None	None	None	None	N
P/D	0.5796	likely_pathogenic	0.7009	pathogenic	-0.3	Destabilizing	None	N	0.157	neutral	None	None	None	None	N
P/E	0.4419	ambiguous	0.5486	ambiguous	-0.415	Destabilizing	0.019	N	0.349	neutral	None	None	None	None	N
P/F	0.6941	likely_pathogenic	0.8146	pathogenic	-0.674	Destabilizing	0.985	D	0.319	neutral	None	None	None	None	N
P/G	0.3978	ambiguous	0.531	ambiguous	-0.368	Destabilizing	0.2	N	0.305	neutral	None	None	None	None	N
P/H	0.3435	ambiguous	0.4725	ambiguous	0.026	Stabilizing	0.858	D	0.299	neutral	N	0.484033715	None	None	N
P/I	0.4598	ambiguous	0.6221	pathogenic	-0.273	Destabilizing	0.955	D	0.358	neutral	None	None	None	None	N
P/K	0.4856	ambiguous	0.6078	pathogenic	-0.344	Destabilizing	0.383	N	0.327	neutral	None	None	None	None	N
P/L	0.189	likely_benign	0.2749	benign	-0.273	Destabilizing	0.694	D	0.363	neutral	D	0.532576755	None	None	N
P/M	0.4355	ambiguous	0.5782	pathogenic	-0.528	Destabilizing	0.889	D	0.297	neutral	None	None	None	None	N
P/N	0.4214	ambiguous	0.5695	pathogenic	-0.137	Destabilizing	0.272	N	0.373	neutral	None	None	None	None	N
P/Q	0.2354	likely_benign	0.3359	benign	-0.344	Destabilizing	0.015	N	0.201	neutral	None	None	None	None	N
P/R	0.3635	ambiguous	0.4691	ambiguous	0.094	Stabilizing	0.03	N	0.246	neutral	N	0.500848338	None	None	N
P/S	0.1619	likely_benign	0.242	benign	-0.445	Destabilizing	0.116	N	0.319	neutral	N	0.476798043	None	None	N
P/T	0.1444	likely_benign	0.2198	benign	-0.466	Destabilizing	0.22	N	0.319	neutral	N	0.495693235	None	None	N
P/V	0.3075	likely_benign	0.4299	ambiguous	-0.254	Destabilizing	0.345	N	0.329	neutral	None	None	None	None	N
P/W	0.8244	likely_pathogenic	0.899	pathogenic	-0.742	Destabilizing	0.996	D	0.37	neutral	None	None	None	None	N
P/Y	0.6631	likely_pathogenic	0.7829	pathogenic	-0.458	Destabilizing	0.985	D	0.321	neutral	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.