TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14792	44599;44600;44601	chr2:178629351;178629350;178629349	chr2:179494078;179494077;179494076
N2AB	13151	39676;39677;39678	chr2:178629351;178629350;178629349	chr2:179494078;179494077;179494076
N2A	12224	36895;36896;36897	chr2:178629351;178629350;178629349	chr2:179494078;179494077;179494076
N2B	5727	17404;17405;17406	chr2:178629351;178629350;178629349	chr2:179494078;179494077;179494076
Novex-1	5852	17779;17780;17781	chr2:178629351;178629350;178629349	chr2:179494078;179494077;179494076
Novex-2	5919	17980;17981;17982	chr2:178629351;178629350;178629349	chr2:179494078;179494077;179494076
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: Ig-99
• Domain position: 28
• Structural Position: 44
• Q(SASA): 0.1736
• 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	rs536313527	None	0.998	D	0.607	0.448	0.733197302235	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.94024E-04	None	0	0	0	0	0
I/F	rs536313527	None	0.998	D	0.607	0.448	0.733197302235	gnomAD-4.0.0	1.31377E-05	None	None	None	None	N	None	0	0	None	0	3.88954E-04	None	0	0	0	0	0
I/M	None	None	0.998	N	0.579	0.226	0.596816321548	gnomAD-4.0.0	6.84613E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99836E-07	0	0
I/N	rs747654057	-2.055	0.999	D	0.722	0.534	0.887531180484	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.22E-05	0
I/N	rs747654057	-2.055	0.999	D	0.722	0.534	0.887531180484	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/N	rs747654057	-2.055	0.999	D	0.722	0.534	0.887531180484	gnomAD-4.0.0	3.53426E-05	None	None	None	None	N	None	0	3.33578E-05	None	0	0	None	0	0	4.40942E-05	0	4.80692E-05
I/T	rs747654057	-2.448	0.989	N	0.605	0.471	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	1.93899E-04	0	None	0	0	None	0	None	0	8.89E-06	0
I/T	rs747654057	-2.448	0.989	N	0.605	0.471	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20621E-04	0	0	0	0	None	0	0	0	0	0
I/T	rs747654057	-2.448	0.989	N	0.605	0.471	None	gnomAD-4.0.0	6.8205E-06	None	None	None	None	N	None	1.33547E-04	0	None	0	0	None	0	0	8.47965E-07	0	0
I/V	None	None	0.333	N	0.211	0.194	0.577073266457	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25002E-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	0.8376	likely_pathogenic	0.8565	pathogenic	-1.911	Destabilizing	0.992	D	0.471	neutral	None	None	None	None	N
I/C	0.9279	likely_pathogenic	0.9316	pathogenic	-0.973	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	N
I/D	0.95	likely_pathogenic	0.9636	pathogenic	-1.62	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
I/E	0.9309	likely_pathogenic	0.9494	pathogenic	-1.545	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
I/F	0.4245	ambiguous	0.4804	ambiguous	-1.254	Destabilizing	0.998	D	0.607	neutral	D	0.551104527	None	None	N
I/G	0.9611	likely_pathogenic	0.9656	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
I/H	0.8941	likely_pathogenic	0.9167	pathogenic	-1.559	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
I/K	0.873	likely_pathogenic	0.9025	pathogenic	-1.318	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
I/L	0.2589	likely_benign	0.2878	benign	-0.859	Destabilizing	0.889	D	0.429	neutral	N	0.502561039	None	None	N
I/M	0.2881	likely_benign	0.3241	benign	-0.617	Destabilizing	0.998	D	0.579	neutral	N	0.510311447	None	None	N
I/N	0.6879	likely_pathogenic	0.7319	pathogenic	-1.237	Destabilizing	0.999	D	0.722	prob.delet.	D	0.595347389	None	None	N
I/P	0.9581	likely_pathogenic	0.9648	pathogenic	-1.182	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
I/Q	0.89	likely_pathogenic	0.9097	pathogenic	-1.329	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
I/R	0.8235	likely_pathogenic	0.8625	pathogenic	-0.803	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
I/S	0.7229	likely_pathogenic	0.7537	pathogenic	-1.841	Destabilizing	0.998	D	0.637	neutral	N	0.507580693	None	None	N
I/T	0.6779	likely_pathogenic	0.7095	pathogenic	-1.641	Destabilizing	0.989	D	0.605	neutral	N	0.495204238	None	None	N
I/V	0.1758	likely_benign	0.1744	benign	-1.182	Destabilizing	0.333	N	0.211	neutral	N	0.416563306	None	None	N
I/W	0.9608	likely_pathogenic	0.9668	pathogenic	-1.436	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
I/Y	0.83	likely_pathogenic	0.8626	pathogenic	-1.179	Destabilizing	1.0	D	0.634	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.