TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6028	18307;18308;18309	chr2:178730318;178730317;178730316	chr2:179595045;179595044;179595043
N2AB	5711	17356;17357;17358	chr2:178730318;178730317;178730316	chr2:179595045;179595044;179595043
N2A	4784	14575;14576;14577	chr2:178730318;178730317;178730316	chr2:179595045;179595044;179595043
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-44
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4852
• 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
R/G	rs766799309	-1.092	0.98	N	0.533	0.269	0.388812400583	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	2.94E-05	None	0	0	None	0	None	0	0	0
R/G	rs766799309	-1.092	0.98	N	0.533	0.269	0.388812400583	gnomAD-4.0.0	2.05599E-06	None	None	None	None	N	None	0	2.25073E-05	None	0	0	None	0	0	1.80081E-06	0	0
R/K	rs552189742	-0.396	0.122	N	0.163	0.128	0.130388298395	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	5.74E-05	None	0	None	0	0	0
R/K	rs552189742	-0.396	0.122	N	0.163	0.128	0.130388298395	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	3.85654E-04	None	0	0	0	0	0
R/K	rs552189742	-0.396	0.122	N	0.163	0.128	0.130388298395	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	2E-03	0	None	None	None	0	None
R/K	rs552189742	-0.396	0.122	N	0.163	0.128	0.130388298395	gnomAD-4.0.0	1.31404E-05	None	None	None	None	N	None	0	0	None	0	3.86548E-04	None	0	0	0	0	0
R/S	rs775372762	-0.759	0.961	N	0.523	0.279	0.204665344411	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.12E-06	0
R/T	rs552189742	None	0.98	N	0.545	0.279	0.369867359543	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/T	rs552189742	None	0.98	N	0.545	0.279	0.369867359543	gnomAD-4.0.0	6.57531E-06	None	None	None	None	N	None	2.41569E-05	0	None	0	0	None	0	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
R/A	0.2823	likely_benign	0.3162	benign	-0.419	Destabilizing	0.931	D	0.528	neutral	None	None	None	None	N
R/C	0.2419	likely_benign	0.2812	benign	-0.418	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
R/D	0.5738	likely_pathogenic	0.6222	pathogenic	0.078	Stabilizing	0.996	D	0.531	neutral	None	None	None	None	N
R/E	0.3407	ambiguous	0.3724	ambiguous	0.204	Stabilizing	0.97	D	0.494	neutral	None	None	None	None	N
R/F	0.5195	ambiguous	0.5716	pathogenic	-0.261	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
R/G	0.222	likely_benign	0.2485	benign	-0.723	Destabilizing	0.98	D	0.533	neutral	N	0.493745355	None	None	N
R/H	0.116	likely_benign	0.1255	benign	-1.131	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	N
R/I	0.238	likely_benign	0.2882	benign	0.388	Stabilizing	0.999	D	0.63	neutral	None	None	None	None	N
R/K	0.103	likely_benign	0.115	benign	-0.416	Destabilizing	0.122	N	0.163	neutral	N	0.429309874	None	None	N
R/L	0.2213	likely_benign	0.2511	benign	0.388	Stabilizing	0.985	D	0.533	neutral	None	None	None	None	N
R/M	0.246	likely_benign	0.2813	benign	-0.093	Destabilizing	1.0	D	0.589	neutral	N	0.498940531	None	None	N
R/N	0.4622	ambiguous	0.5306	ambiguous	-0.031	Destabilizing	0.985	D	0.518	neutral	None	None	None	None	N
R/P	0.2931	likely_benign	0.341	ambiguous	0.141	Stabilizing	0.999	D	0.604	neutral	None	None	None	None	N
R/Q	0.1188	likely_benign	0.1276	benign	-0.117	Destabilizing	0.97	D	0.551	neutral	None	None	None	None	N
R/S	0.3807	ambiguous	0.4178	ambiguous	-0.652	Destabilizing	0.961	D	0.523	neutral	N	0.422381115	None	None	N
R/T	0.1736	likely_benign	0.1961	benign	-0.343	Destabilizing	0.98	D	0.545	neutral	N	0.378918339	None	None	N
R/V	0.2936	likely_benign	0.3362	benign	0.141	Stabilizing	0.996	D	0.544	neutral	None	None	None	None	N
R/W	0.1873	likely_benign	0.2016	benign	-0.04	Destabilizing	1.0	D	0.724	prob.delet.	N	0.457008787	None	None	N
R/Y	0.4035	ambiguous	0.4517	ambiguous	0.28	Stabilizing	0.999	D	0.627	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.