TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21803	65632;65633;65634	chr2:178583775;178583774;178583773	chr2:179448502;179448501;179448500
N2AB	20162	60709;60710;60711	chr2:178583775;178583774;178583773	chr2:179448502;179448501;179448500
N2A	19235	57928;57929;57930	chr2:178583775;178583774;178583773	chr2:179448502;179448501;179448500
N2B	12738	38437;38438;38439	chr2:178583775;178583774;178583773	chr2:179448502;179448501;179448500
Novex-1	12863	38812;38813;38814	chr2:178583775;178583774;178583773	chr2:179448502;179448501;179448500
Novex-2	12930	39013;39014;39015	chr2:178583775;178583774;178583773	chr2:179448502;179448501;179448500
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-46
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7798
• 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
K/R	None	None	0.41	N	0.535	0.126	0.222439326576	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/T	rs2048309985	None	0.83	N	0.507	0.251	0.352476196916	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs2048309985	None	0.83	N	0.507	0.251	0.352476196916	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	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
K/A	0.3334	likely_benign	0.3114	benign	0.063	Stabilizing	0.48	N	0.523	neutral	None	None	None	None	N
K/C	0.7149	likely_pathogenic	0.6373	pathogenic	-0.117	Destabilizing	0.993	D	0.708	prob.delet.	None	None	None	None	N
K/D	0.545	ambiguous	0.5286	ambiguous	-0.009	Destabilizing	0.866	D	0.497	neutral	None	None	None	None	N
K/E	0.2172	likely_benign	0.1994	benign	0.001	Stabilizing	0.41	N	0.541	neutral	N	0.414082211	None	None	N
K/F	0.8225	likely_pathogenic	0.7743	pathogenic	-0.12	Destabilizing	0.993	D	0.634	neutral	None	None	None	None	N
K/G	0.4543	ambiguous	0.4421	ambiguous	-0.137	Destabilizing	0.866	D	0.455	neutral	None	None	None	None	N
K/H	0.3195	likely_benign	0.2648	benign	-0.392	Destabilizing	0.961	D	0.572	neutral	None	None	None	None	N
K/I	0.4125	ambiguous	0.3598	ambiguous	0.513	Stabilizing	0.908	D	0.633	neutral	N	0.497471598	None	None	N
K/L	0.4231	ambiguous	0.3763	ambiguous	0.513	Stabilizing	0.866	D	0.455	neutral	None	None	None	None	N
K/M	0.3216	likely_benign	0.2798	benign	0.21	Stabilizing	0.98	D	0.577	neutral	None	None	None	None	N
K/N	0.3901	ambiguous	0.3621	ambiguous	0.273	Stabilizing	0.83	D	0.575	neutral	N	0.475421458	None	None	N
K/P	0.6129	likely_pathogenic	0.78	pathogenic	0.391	Stabilizing	0.929	D	0.53	neutral	None	None	None	None	N
K/Q	0.1422	likely_benign	0.1228	benign	0.127	Stabilizing	0.01	N	0.352	neutral	N	0.475074741	None	None	N
K/R	0.0869	likely_benign	0.0773	benign	-0.033	Destabilizing	0.41	N	0.535	neutral	N	0.450197726	None	None	N
K/S	0.3818	ambiguous	0.3553	ambiguous	-0.155	Destabilizing	0.48	N	0.554	neutral	None	None	None	None	N
K/T	0.1644	likely_benign	0.1488	benign	-0.002	Destabilizing	0.83	D	0.507	neutral	N	0.440943525	None	None	N
K/V	0.354	ambiguous	0.312	benign	0.391	Stabilizing	0.866	D	0.541	neutral	None	None	None	None	N
K/W	0.8436	likely_pathogenic	0.8042	pathogenic	-0.172	Destabilizing	0.993	D	0.723	prob.delet.	None	None	None	None	N
K/Y	0.6977	likely_pathogenic	0.6265	pathogenic	0.176	Stabilizing	0.929	D	0.579	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.