TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31206	93841;93842;93843	chr2:178548010;178548009;178548008	chr2:179412737;179412736;179412735
N2AB	29565	88918;88919;88920	chr2:178548010;178548009;178548008	chr2:179412737;179412736;179412735
N2A	28638	86137;86138;86139	chr2:178548010;178548009;178548008	chr2:179412737;179412736;179412735
N2B	22141	66646;66647;66648	chr2:178548010;178548009;178548008	chr2:179412737;179412736;179412735
Novex-1	22266	67021;67022;67023	chr2:178548010;178548009;178548008	chr2:179412737;179412736;179412735
Novex-2	22333	67222;67223;67224	chr2:178548010;178548009;178548008	chr2:179412737;179412736;179412735
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: Fn3-115
• Domain position: 94
• Structural Position: 130
• Q(SASA): 0.0449
• 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/F	None	None	0.981	N	0.669	0.176	0.624369413046	gnomAD-4.0.0	6.84218E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99468E-07	0	0
I/L	rs1020011607	None	0.39	N	0.432	0.06	0.488266720666	gnomAD-4.0.0	2.05265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79894E-06	0	1.65656E-05

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	0.796	likely_pathogenic	0.8327	pathogenic	-3.014	Highly Destabilizing	0.825	D	0.579	neutral	None	None	None	None	N
I/C	0.8694	likely_pathogenic	0.8911	pathogenic	-2.816	Highly Destabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	N
I/D	0.9984	likely_pathogenic	0.9983	pathogenic	-3.656	Highly Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
I/E	0.9949	likely_pathogenic	0.9944	pathogenic	-3.425	Highly Destabilizing	0.985	D	0.789	deleterious	None	None	None	None	N
I/F	0.7857	likely_pathogenic	0.761	pathogenic	-1.716	Destabilizing	0.981	D	0.669	prob.neutral	N	0.483042529	None	None	N
I/G	0.9844	likely_pathogenic	0.9867	pathogenic	-3.507	Highly Destabilizing	0.985	D	0.779	deleterious	None	None	None	None	N
I/H	0.9948	likely_pathogenic	0.994	pathogenic	-2.725	Highly Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
I/K	0.9905	likely_pathogenic	0.988	pathogenic	-2.299	Highly Destabilizing	0.985	D	0.785	deleterious	None	None	None	None	N
I/L	0.3658	ambiguous	0.3556	ambiguous	-1.561	Destabilizing	0.39	N	0.432	neutral	N	0.485740026	None	None	N
I/M	0.3934	ambiguous	0.3886	ambiguous	-1.964	Destabilizing	0.981	D	0.606	neutral	N	0.488513759	None	None	N
I/N	0.9684	likely_pathogenic	0.9696	pathogenic	-2.784	Highly Destabilizing	0.994	D	0.773	deleterious	N	0.484056487	None	None	N
I/P	0.9518	likely_pathogenic	0.9534	pathogenic	-2.033	Highly Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
I/Q	0.9868	likely_pathogenic	0.9853	pathogenic	-2.644	Highly Destabilizing	0.995	D	0.766	deleterious	None	None	None	None	N
I/R	0.9811	likely_pathogenic	0.9772	pathogenic	-1.982	Destabilizing	0.995	D	0.767	deleterious	None	None	None	None	N
I/S	0.9153	likely_pathogenic	0.9272	pathogenic	-3.396	Highly Destabilizing	0.981	D	0.687	prob.delet.	N	0.483296019	None	None	N
I/T	0.8527	likely_pathogenic	0.8804	pathogenic	-3.029	Highly Destabilizing	0.877	D	0.646	neutral	N	0.443992191	None	None	N
I/V	0.1072	likely_benign	0.1164	benign	-2.033	Highly Destabilizing	0.009	N	0.197	neutral	N	0.422499411	None	None	N
I/W	0.9941	likely_pathogenic	0.9929	pathogenic	-1.985	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
I/Y	0.9856	likely_pathogenic	0.9825	pathogenic	-1.868	Destabilizing	0.995	D	0.643	neutral	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.