TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23506	70741;70742;70743	chr2:178575616;178575615;178575614	chr2:179440343;179440342;179440341
N2AB	21865	65818;65819;65820	chr2:178575616;178575615;178575614	chr2:179440343;179440342;179440341
N2A	20938	63037;63038;63039	chr2:178575616;178575615;178575614	chr2:179440343;179440342;179440341
N2B	14441	43546;43547;43548	chr2:178575616;178575615;178575614	chr2:179440343;179440342;179440341
Novex-1	14566	43921;43922;43923	chr2:178575616;178575615;178575614	chr2:179440343;179440342;179440341
Novex-2	14633	44122;44123;44124	chr2:178575616;178575615;178575614	chr2:179440343;179440342;179440341
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-58
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.2054
• 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
F/L	rs753350142	-1.595	0.001	N	0.275	0.294	0.548654159409	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
F/L	rs753350142	-1.595	0.001	N	0.275	0.294	0.548654159409	gnomAD-4.0.0	1.59165E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85909E-06	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
F/A	0.8407	likely_pathogenic	0.882	pathogenic	-2.852	Highly Destabilizing	0.345	N	0.592	neutral	None	None	None	None	N
F/C	0.3834	ambiguous	0.3972	ambiguous	-1.349	Destabilizing	0.987	D	0.647	neutral	N	0.498951679	None	None	N
F/D	0.9533	likely_pathogenic	0.972	pathogenic	-2.955	Highly Destabilizing	0.965	D	0.645	neutral	None	None	None	None	N
F/E	0.9647	likely_pathogenic	0.9755	pathogenic	-2.778	Highly Destabilizing	0.722	D	0.643	neutral	None	None	None	None	N
F/G	0.9255	likely_pathogenic	0.9431	pathogenic	-3.235	Highly Destabilizing	0.722	D	0.585	neutral	None	None	None	None	N
F/H	0.5683	likely_pathogenic	0.6261	pathogenic	-1.73	Destabilizing	0.818	D	0.59	neutral	None	None	None	None	N
F/I	0.4525	ambiguous	0.5453	ambiguous	-1.599	Destabilizing	0.166	N	0.558	neutral	N	0.466473901	None	None	N
F/K	0.9405	likely_pathogenic	0.9551	pathogenic	-1.668	Destabilizing	0.722	D	0.628	neutral	None	None	None	None	N
F/L	0.8774	likely_pathogenic	0.9041	pathogenic	-1.599	Destabilizing	0.001	N	0.275	neutral	N	0.478960408	None	None	N
F/M	0.7089	likely_pathogenic	0.7501	pathogenic	-1.211	Destabilizing	0.818	D	0.559	neutral	None	None	None	None	N
F/N	0.774	likely_pathogenic	0.8364	pathogenic	-2.022	Highly Destabilizing	0.901	D	0.646	neutral	None	None	None	None	N
F/P	0.9985	likely_pathogenic	0.999	pathogenic	-2.027	Highly Destabilizing	0.965	D	0.648	neutral	None	None	None	None	N
F/Q	0.8819	likely_pathogenic	0.9033	pathogenic	-2.048	Highly Destabilizing	0.965	D	0.652	neutral	None	None	None	None	N
F/R	0.844	likely_pathogenic	0.8744	pathogenic	-1.141	Destabilizing	0.901	D	0.641	neutral	None	None	None	None	N
F/S	0.6714	likely_pathogenic	0.7442	pathogenic	-2.621	Highly Destabilizing	0.662	D	0.59	neutral	N	0.475880031	None	None	N
F/T	0.7729	likely_pathogenic	0.8346	pathogenic	-2.352	Highly Destabilizing	0.561	D	0.596	neutral	None	None	None	None	N
F/V	0.4307	ambiguous	0.513	ambiguous	-2.027	Highly Destabilizing	0.166	N	0.564	neutral	N	0.476034746	None	None	N
F/W	0.5827	likely_pathogenic	0.6226	pathogenic	-0.511	Destabilizing	0.901	D	0.595	neutral	None	None	None	None	N
F/Y	0.079	likely_benign	0.0889	benign	-0.869	Destabilizing	None	N	0.238	neutral	N	0.409908542	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.