TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24841	74746;74747;74748	chr2:178571611;178571610;178571609	chr2:179436338;179436337;179436336
N2AB	23200	69823;69824;69825	chr2:178571611;178571610;178571609	chr2:179436338;179436337;179436336
N2A	22273	67042;67043;67044	chr2:178571611;178571610;178571609	chr2:179436338;179436337;179436336
N2B	15776	47551;47552;47553	chr2:178571611;178571610;178571609	chr2:179436338;179436337;179436336
Novex-1	15901	47926;47927;47928	chr2:178571611;178571610;178571609	chr2:179436338;179436337;179436336
Novex-2	15968	48127;48128;48129	chr2:178571611;178571610;178571609	chr2:179436338;179436337;179436336
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-68
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.2471
• 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
I/T	rs1382387828	None	0.892	D	0.781	0.5	0.728227171412	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
I/A	0.9766	likely_pathogenic	0.9738	pathogenic	-2.406	Highly Destabilizing	0.845	D	0.675	prob.neutral	None	None	None	None	I
I/C	0.9781	likely_pathogenic	0.9747	pathogenic	-1.826	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
I/D	0.999	likely_pathogenic	0.9991	pathogenic	-2.536	Highly Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	I
I/E	0.9956	likely_pathogenic	0.9953	pathogenic	-2.481	Highly Destabilizing	0.987	D	0.831	deleterious	None	None	None	None	I
I/F	0.9485	likely_pathogenic	0.9392	pathogenic	-1.863	Destabilizing	0.967	D	0.746	deleterious	D	0.53753897	None	None	I
I/G	0.997	likely_pathogenic	0.9965	pathogenic	-2.799	Highly Destabilizing	0.987	D	0.829	deleterious	None	None	None	None	I
I/H	0.9973	likely_pathogenic	0.997	pathogenic	-2.011	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
I/K	0.987	likely_pathogenic	0.9866	pathogenic	-1.783	Destabilizing	0.987	D	0.829	deleterious	None	None	None	None	I
I/L	0.4247	ambiguous	0.3936	ambiguous	-1.343	Destabilizing	0.426	N	0.421	neutral	N	0.474819187	None	None	I
I/M	0.6285	likely_pathogenic	0.5796	pathogenic	-1.06	Destabilizing	0.983	D	0.705	prob.neutral	D	0.528717559	None	None	I
I/N	0.9822	likely_pathogenic	0.9819	pathogenic	-1.785	Destabilizing	0.994	D	0.833	deleterious	D	0.529731517	None	None	I
I/P	0.9702	likely_pathogenic	0.9674	pathogenic	-1.672	Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	I
I/Q	0.9927	likely_pathogenic	0.9918	pathogenic	-1.96	Destabilizing	0.996	D	0.828	deleterious	None	None	None	None	I
I/R	0.983	likely_pathogenic	0.9821	pathogenic	-1.121	Destabilizing	0.987	D	0.834	deleterious	None	None	None	None	I
I/S	0.9834	likely_pathogenic	0.9819	pathogenic	-2.424	Highly Destabilizing	0.983	D	0.807	deleterious	D	0.540327354	None	None	I
I/T	0.947	likely_pathogenic	0.9452	pathogenic	-2.244	Highly Destabilizing	0.892	D	0.781	deleterious	D	0.528971049	None	None	I
I/V	0.0975	likely_benign	0.0975	benign	-1.672	Destabilizing	0.011	N	0.242	neutral	N	0.494511438	None	None	I
I/W	0.998	likely_pathogenic	0.9978	pathogenic	-2.016	Highly Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
I/Y	0.9934	likely_pathogenic	0.9926	pathogenic	-1.799	Destabilizing	0.987	D	0.78	deleterious	None	None	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.