TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24194	72805;72806;72807	chr2:178573552;178573551;178573550	chr2:179438279;179438278;179438277
N2AB	22553	67882;67883;67884	chr2:178573552;178573551;178573550	chr2:179438279;179438278;179438277
N2A	21626	65101;65102;65103	chr2:178573552;178573551;178573550	chr2:179438279;179438278;179438277
N2B	15129	45610;45611;45612	chr2:178573552;178573551;178573550	chr2:179438279;179438278;179438277
Novex-1	15254	45985;45986;45987	chr2:178573552;178573551;178573550	chr2:179438279;179438278;179438277
Novex-2	15321	46186;46187;46188	chr2:178573552;178573551;178573550	chr2:179438279;179438278;179438277
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-63
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1496
• 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/L	rs746396020	-1.114	0.084	N	0.443	0.078	0.539835882356	gnomAD-2.1.1	5.96E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.19E-05	0
I/L	rs746396020	-1.114	0.084	N	0.443	0.078	0.539835882356	gnomAD-4.0.0	1.95229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.37687E-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	0.388	ambiguous	0.4898	ambiguous	-2.755	Highly Destabilizing	0.404	N	0.629	neutral	None	None	None	None	N
I/C	0.5598	ambiguous	0.6188	pathogenic	-1.777	Destabilizing	0.973	D	0.694	prob.neutral	None	None	None	None	N
I/D	0.7925	likely_pathogenic	0.8764	pathogenic	-3.209	Highly Destabilizing	0.906	D	0.775	deleterious	None	None	None	None	N
I/E	0.6193	likely_pathogenic	0.7395	pathogenic	-2.952	Highly Destabilizing	0.906	D	0.739	prob.delet.	None	None	None	None	N
I/F	0.224	likely_benign	0.2873	benign	-1.563	Destabilizing	0.826	D	0.63	neutral	None	None	None	None	N
I/G	0.6734	likely_pathogenic	0.7751	pathogenic	-3.279	Highly Destabilizing	0.906	D	0.731	prob.delet.	None	None	None	None	N
I/H	0.5109	ambiguous	0.6035	pathogenic	-2.791	Highly Destabilizing	0.991	D	0.766	deleterious	None	None	None	None	N
I/K	0.4432	ambiguous	0.5611	ambiguous	-1.962	Destabilizing	0.879	D	0.743	deleterious	N	0.493447071	None	None	N
I/L	0.107	likely_benign	0.1255	benign	-1.2	Destabilizing	0.084	N	0.443	neutral	N	0.463318952	None	None	N
I/M	0.1239	likely_benign	0.1443	benign	-1.254	Destabilizing	0.782	D	0.655	neutral	N	0.466836108	None	None	N
I/N	0.3175	likely_benign	0.4321	ambiguous	-2.413	Highly Destabilizing	0.967	D	0.786	deleterious	None	None	None	None	N
I/P	0.9729	likely_pathogenic	0.9806	pathogenic	-1.707	Destabilizing	0.967	D	0.778	deleterious	None	None	None	None	N
I/Q	0.423	ambiguous	0.5175	ambiguous	-2.199	Highly Destabilizing	0.967	D	0.781	deleterious	None	None	None	None	N
I/R	0.3526	ambiguous	0.4434	ambiguous	-1.783	Destabilizing	0.879	D	0.785	deleterious	N	0.498642247	None	None	N
I/S	0.296	likely_benign	0.3852	ambiguous	-2.995	Highly Destabilizing	0.826	D	0.67	neutral	None	None	None	None	N
I/T	0.2143	likely_benign	0.3096	benign	-2.609	Highly Destabilizing	0.505	D	0.663	neutral	N	0.492868281	None	None	N
I/V	0.0674	likely_benign	0.0773	benign	-1.707	Destabilizing	0.001	N	0.277	neutral	N	0.50062376	None	None	N
I/W	0.8544	likely_pathogenic	0.8784	pathogenic	-1.986	Destabilizing	0.991	D	0.712	prob.delet.	None	None	None	None	N
I/Y	0.5415	ambiguous	0.612	pathogenic	-1.771	Destabilizing	0.906	D	0.717	prob.delet.	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.