TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13685	41278;41279;41280	chr2:178636674;178636673;178636672	chr2:179501401;179501400;179501399
N2AB	12044	36355;36356;36357	chr2:178636674;178636673;178636672	chr2:179501401;179501400;179501399
N2A	11117	33574;33575;33576	chr2:178636674;178636673;178636672	chr2:179501401;179501400;179501399
N2B	4620	14083;14084;14085	chr2:178636674;178636673;178636672	chr2:179501401;179501400;179501399
Novex-1	4745	14458;14459;14460	chr2:178636674;178636673;178636672	chr2:179501401;179501400;179501399
Novex-2	4812	14659;14660;14661	chr2:178636674;178636673;178636672	chr2:179501401;179501400;179501399
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: Ig-87
• Domain position: 2
• Structural Position: 3
• Q(SASA): 0.896
• Predicted PPI site: I

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/S	None	None	1.0	D	0.6	0.834	0.87862966783	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9985	likely_pathogenic	0.9986	pathogenic	-2.696	Highly Destabilizing	1.0	D	0.555	neutral	None	None	None	None	I
F/C	0.9984	likely_pathogenic	0.9986	pathogenic	-1.401	Destabilizing	1.0	D	0.699	prob.neutral	D	0.749959085	None	None	I
F/D	0.9993	likely_pathogenic	0.9995	pathogenic	-1.889	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
F/E	0.9995	likely_pathogenic	0.9996	pathogenic	-1.776	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
F/G	0.9991	likely_pathogenic	0.9993	pathogenic	-3.058	Highly Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
F/H	0.9977	likely_pathogenic	0.9983	pathogenic	-1.252	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
F/I	0.9799	likely_pathogenic	0.9725	pathogenic	-1.568	Destabilizing	1.0	D	0.594	neutral	D	0.531456919	None	None	I
F/K	0.9996	likely_pathogenic	0.9997	pathogenic	-1.476	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
F/L	0.9985	likely_pathogenic	0.9985	pathogenic	-1.568	Destabilizing	0.999	D	0.504	neutral	D	0.608181954	None	None	I
F/M	0.9884	likely_pathogenic	0.9876	pathogenic	-1.217	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
F/N	0.9985	likely_pathogenic	0.9986	pathogenic	-1.549	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
F/P	0.9999	likely_pathogenic	0.9998	pathogenic	-1.944	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
F/Q	0.9995	likely_pathogenic	0.9996	pathogenic	-1.68	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
F/R	0.9991	likely_pathogenic	0.9993	pathogenic	-0.754	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
F/S	0.9992	likely_pathogenic	0.9993	pathogenic	-2.343	Highly Destabilizing	1.0	D	0.6	neutral	D	0.748970916	None	None	I
F/T	0.9986	likely_pathogenic	0.9989	pathogenic	-2.14	Highly Destabilizing	1.0	D	0.6	neutral	None	None	None	None	I
F/V	0.9854	likely_pathogenic	0.9829	pathogenic	-1.944	Destabilizing	1.0	D	0.567	neutral	D	0.66072514	None	None	I
F/W	0.9519	likely_pathogenic	0.9646	pathogenic	-0.494	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
F/Y	0.8442	likely_pathogenic	0.8587	pathogenic	-0.776	Destabilizing	0.999	D	0.519	neutral	D	0.708727326	None	None	I

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.