TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33074	99445;99446;99447	chr2:178538609;178538608;178538607	chr2:179403336;179403335;179403334
N2AB	31433	94522;94523;94524	chr2:178538609;178538608;178538607	chr2:179403336;179403335;179403334
N2A	30506	91741;91742;91743	chr2:178538609;178538608;178538607	chr2:179403336;179403335;179403334
N2B	24009	72250;72251;72252	chr2:178538609;178538608;178538607	chr2:179403336;179403335;179403334
Novex-1	24134	72625;72626;72627	chr2:178538609;178538608;178538607	chr2:179403336;179403335;179403334
Novex-2	24201	72826;72827;72828	chr2:178538609;178538608;178538607	chr2:179403336;179403335;179403334
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-129
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.0775
• 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	rs1692851858	None	0.454	N	0.735	0.18	0.366277470483	gnomAD-4.0.0	1.59164E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	None	0	0	0	0	0
F/S	rs1328730203	None	0.051	N	0.53	0.295	0.512942373286	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
F/S	rs1328730203	None	0.051	N	0.53	0.295	0.512942373286	gnomAD-4.0.0	2.47887E-06	None	None	None	None	N	None	5.33974E-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
F/A	0.6985	likely_pathogenic	0.7549	pathogenic	-3.002	Highly Destabilizing	0.525	D	0.718	prob.delet.	None	None	None	None	N
F/C	0.4608	ambiguous	0.5388	ambiguous	-1.582	Destabilizing	0.997	D	0.74	deleterious	N	0.518076157	None	None	N
F/D	0.9723	likely_pathogenic	0.977	pathogenic	-3.132	Highly Destabilizing	0.949	D	0.75	deleterious	None	None	None	None	N
F/E	0.9658	likely_pathogenic	0.9713	pathogenic	-2.967	Highly Destabilizing	0.949	D	0.755	deleterious	None	None	None	None	N
F/G	0.9208	likely_pathogenic	0.9406	pathogenic	-3.395	Highly Destabilizing	0.728	D	0.748	deleterious	None	None	None	None	N
F/H	0.7489	likely_pathogenic	0.8002	pathogenic	-1.772	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
F/I	0.3488	ambiguous	0.3879	ambiguous	-1.72	Destabilizing	0.051	N	0.54	neutral	N	0.469532849	None	None	N
F/K	0.9529	likely_pathogenic	0.9584	pathogenic	-1.988	Destabilizing	0.949	D	0.75	deleterious	None	None	None	None	N
F/L	0.8299	likely_pathogenic	0.8718	pathogenic	-1.72	Destabilizing	0.454	N	0.735	prob.delet.	N	0.466127184	None	None	N
F/M	0.5678	likely_pathogenic	0.6088	pathogenic	-1.251	Destabilizing	0.974	D	0.781	deleterious	None	None	None	None	N
F/N	0.8485	likely_pathogenic	0.8761	pathogenic	-2.302	Highly Destabilizing	0.949	D	0.763	deleterious	None	None	None	None	N
F/P	0.9991	likely_pathogenic	0.9993	pathogenic	-2.157	Highly Destabilizing	0.974	D	0.796	deleterious	None	None	None	None	N
F/Q	0.8967	likely_pathogenic	0.9155	pathogenic	-2.357	Highly Destabilizing	0.974	D	0.787	deleterious	None	None	None	None	N
F/R	0.8994	likely_pathogenic	0.9094	pathogenic	-1.33	Destabilizing	0.949	D	0.793	deleterious	None	None	None	None	N
F/S	0.573	likely_pathogenic	0.6465	pathogenic	-2.929	Highly Destabilizing	0.051	N	0.53	neutral	N	0.449330935	None	None	N
F/T	0.6307	likely_pathogenic	0.6878	pathogenic	-2.673	Highly Destabilizing	0.728	D	0.725	prob.delet.	None	None	None	None	N
F/V	0.356	ambiguous	0.4129	ambiguous	-2.157	Highly Destabilizing	0.669	D	0.736	prob.delet.	N	0.480864563	None	None	N
F/W	0.6552	likely_pathogenic	0.6831	pathogenic	-0.622	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
F/Y	0.2543	likely_benign	0.2729	benign	-1.006	Destabilizing	0.961	D	0.699	prob.neutral	N	0.500431759	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.