TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5975	18148;18149;18150	chr2:178730610;178730609;178730608	chr2:179595337;179595336;179595335
N2AB	5658	17197;17198;17199	chr2:178730610;178730609;178730608	chr2:179595337;179595336;179595335
N2A	4731	14416;14417;14418	chr2:178730610;178730609;178730608	chr2:179595337;179595336;179595335
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-43
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1591
• 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/V	rs776879045	-1.886	0.98	N	0.579	0.379	0.662754131768	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
F/V	rs776879045	-1.886	0.98	N	0.579	0.379	0.662754131768	gnomAD-4.0.0	1.59157E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85907E-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	0.6635	likely_pathogenic	0.6799	pathogenic	-2.405	Highly Destabilizing	0.871	D	0.591	neutral	None	None	None	None	N
F/C	0.4721	ambiguous	0.4904	ambiguous	-0.96	Destabilizing	1.0	D	0.726	prob.delet.	N	0.474915318	None	None	N
F/D	0.9117	likely_pathogenic	0.9156	pathogenic	-2.012	Highly Destabilizing	0.991	D	0.689	prob.neutral	None	None	None	None	N
F/E	0.8824	likely_pathogenic	0.8851	pathogenic	-1.965	Destabilizing	0.991	D	0.692	prob.neutral	None	None	None	None	N
F/G	0.8835	likely_pathogenic	0.8852	pathogenic	-2.716	Highly Destabilizing	0.97	D	0.656	neutral	None	None	None	None	N
F/H	0.5915	likely_pathogenic	0.5941	pathogenic	-1.194	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
F/I	0.2702	likely_benign	0.3033	benign	-1.453	Destabilizing	0.994	D	0.537	neutral	N	0.465506401	None	None	N
F/K	0.8117	likely_pathogenic	0.8199	pathogenic	-1.032	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
F/L	0.888	likely_pathogenic	0.8933	pathogenic	-1.453	Destabilizing	0.98	D	0.487	neutral	N	0.437685081	None	None	N
F/M	0.5704	likely_pathogenic	0.5806	pathogenic	-0.986	Destabilizing	0.999	D	0.54	neutral	None	None	None	None	N
F/N	0.7079	likely_pathogenic	0.7203	pathogenic	-0.985	Destabilizing	0.991	D	0.74	deleterious	None	None	None	None	N
F/P	0.9992	likely_pathogenic	0.9992	pathogenic	-1.767	Destabilizing	0.996	D	0.779	deleterious	None	None	None	None	N
F/Q	0.7727	likely_pathogenic	0.7719	pathogenic	-1.209	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	N
F/R	0.696	likely_pathogenic	0.7041	pathogenic	-0.297	Destabilizing	0.996	D	0.778	deleterious	None	None	None	None	N
F/S	0.4698	ambiguous	0.4792	ambiguous	-1.631	Destabilizing	0.489	N	0.418	neutral	N	0.361453739	None	None	N
F/T	0.5872	likely_pathogenic	0.5969	pathogenic	-1.495	Destabilizing	0.942	D	0.629	neutral	None	None	None	None	N
F/V	0.2774	likely_benign	0.2999	benign	-1.767	Destabilizing	0.98	D	0.579	neutral	N	0.447382	None	None	N
F/W	0.6655	likely_pathogenic	0.6486	pathogenic	-0.794	Destabilizing	1.0	D	0.53	neutral	None	None	None	None	N
F/Y	0.1964	likely_benign	0.1994	benign	-0.936	Destabilizing	0.993	D	0.521	neutral	N	0.48426552	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.