TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23956	72091;72092;72093	chr2:178574266;178574265;178574264	chr2:179438993;179438992;179438991
N2AB	22315	67168;67169;67170	chr2:178574266;178574265;178574264	chr2:179438993;179438992;179438991
N2A	21388	64387;64388;64389	chr2:178574266;178574265;178574264	chr2:179438993;179438992;179438991
N2B	14891	44896;44897;44898	chr2:178574266;178574265;178574264	chr2:179438993;179438992;179438991
Novex-1	15016	45271;45272;45273	chr2:178574266;178574265;178574264	chr2:179438993;179438992;179438991
Novex-2	15083	45472;45473;45474	chr2:178574266;178574265;178574264	chr2:179438993;179438992;179438991
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-62
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1113
• 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
I/M	rs778594459	-0.912	1.0	D	0.809	0.428	0.640559690875	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	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
I/A	0.91	likely_pathogenic	0.9288	pathogenic	-2.378	Highly Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
I/C	0.9376	likely_pathogenic	0.9441	pathogenic	-1.477	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
I/D	0.9864	likely_pathogenic	0.9862	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
I/E	0.9719	likely_pathogenic	0.9719	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/F	0.7206	likely_pathogenic	0.7496	pathogenic	-1.536	Destabilizing	1.0	D	0.827	deleterious	D	0.534411871	None	None	N
I/G	0.9784	likely_pathogenic	0.9824	pathogenic	-2.844	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/H	0.9734	likely_pathogenic	0.9756	pathogenic	-2.081	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
I/K	0.9612	likely_pathogenic	0.9644	pathogenic	-1.671	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/L	0.2271	likely_benign	0.256	benign	-1.082	Destabilizing	0.993	D	0.405	neutral	N	0.505883225	None	None	N
I/M	0.2693	likely_benign	0.2968	benign	-0.801	Destabilizing	1.0	D	0.809	deleterious	D	0.536946766	None	None	N
I/N	0.7307	likely_pathogenic	0.7351	pathogenic	-1.726	Destabilizing	1.0	D	0.881	deleterious	N	0.521666895	None	None	N
I/P	0.8627	likely_pathogenic	0.8918	pathogenic	-1.489	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
I/Q	0.9617	likely_pathogenic	0.965	pathogenic	-1.762	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/R	0.9552	likely_pathogenic	0.9595	pathogenic	-1.162	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
I/S	0.9155	likely_pathogenic	0.9238	pathogenic	-2.449	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.543783621	None	None	N
I/T	0.8477	likely_pathogenic	0.8621	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.525679366	None	None	N
I/V	0.1173	likely_benign	0.1332	benign	-1.489	Destabilizing	0.993	D	0.382	neutral	N	0.487508108	None	None	N
I/W	0.9892	likely_pathogenic	0.9899	pathogenic	-1.784	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
I/Y	0.9425	likely_pathogenic	0.9428	pathogenic	-1.542	Destabilizing	1.0	D	0.864	deleterious	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.