TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30454	91585;91586;91587	chr2:178551171;178551170;178551169	chr2:179415898;179415897;179415896
N2AB	28813	86662;86663;86664	chr2:178551171;178551170;178551169	chr2:179415898;179415897;179415896
N2A	27886	83881;83882;83883	chr2:178551171;178551170;178551169	chr2:179415898;179415897;179415896
N2B	21389	64390;64391;64392	chr2:178551171;178551170;178551169	chr2:179415898;179415897;179415896
Novex-1	21514	64765;64766;64767	chr2:178551171;178551170;178551169	chr2:179415898;179415897;179415896
Novex-2	21581	64966;64967;64968	chr2:178551171;178551170;178551169	chr2:179415898;179415897;179415896
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: Fn3-110
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1634
• 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/L	None	None	0.294	N	0.417	0.253	0.29385284311	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
I/T	rs878985220	-2.073	0.822	N	0.763	0.515	0.625654597223	gnomAD-2.1.1	7.14E-06	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs878985220	-2.073	0.822	N	0.763	0.515	0.625654597223	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs878985220	-2.073	0.822	N	0.763	0.515	0.625654597223	gnomAD-4.0.0	1.98348E-05	None	None	None	None	I	None	6.68163E-05	0	None	0	0	None	0	0	2.1193E-05	0	3.20266E-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	0.9311	likely_pathogenic	0.947	pathogenic	-2.146	Highly Destabilizing	0.754	D	0.666	neutral	None	None	None	None	I
I/C	0.9785	likely_pathogenic	0.9819	pathogenic	-1.325	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	I
I/D	0.9979	likely_pathogenic	0.9982	pathogenic	-1.834	Destabilizing	0.993	D	0.837	deleterious	None	None	None	None	I
I/E	0.9931	likely_pathogenic	0.9938	pathogenic	-1.78	Destabilizing	0.978	D	0.831	deleterious	None	None	None	None	I
I/F	0.888	likely_pathogenic	0.9021	pathogenic	-1.481	Destabilizing	0.942	D	0.719	prob.delet.	N	0.514990943	None	None	I
I/G	0.9934	likely_pathogenic	0.9947	pathogenic	-2.539	Highly Destabilizing	0.978	D	0.829	deleterious	None	None	None	None	I
I/H	0.9952	likely_pathogenic	0.996	pathogenic	-1.755	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	I
I/K	0.9878	likely_pathogenic	0.9893	pathogenic	-1.531	Destabilizing	0.978	D	0.829	deleterious	None	None	None	None	I
I/L	0.3362	likely_benign	0.3707	ambiguous	-1.097	Destabilizing	0.294	N	0.417	neutral	N	0.489452335	None	None	I
I/M	0.4442	ambiguous	0.4956	ambiguous	-0.813	Destabilizing	0.942	D	0.689	prob.neutral	D	0.528882143	None	None	I
I/N	0.9619	likely_pathogenic	0.9667	pathogenic	-1.422	Destabilizing	0.99	D	0.833	deleterious	D	0.541252407	None	None	I
I/P	0.9538	likely_pathogenic	0.9539	pathogenic	-1.419	Destabilizing	0.993	D	0.836	deleterious	None	None	None	None	I
I/Q	0.9907	likely_pathogenic	0.9917	pathogenic	-1.564	Destabilizing	0.993	D	0.824	deleterious	None	None	None	None	I
I/R	0.9824	likely_pathogenic	0.9847	pathogenic	-0.928	Destabilizing	0.978	D	0.832	deleterious	None	None	None	None	I
I/S	0.9708	likely_pathogenic	0.9767	pathogenic	-2.084	Highly Destabilizing	0.942	D	0.807	deleterious	D	0.529135633	None	None	I
I/T	0.8686	likely_pathogenic	0.8957	pathogenic	-1.909	Destabilizing	0.822	D	0.763	deleterious	N	0.500991746	None	None	I
I/V	0.129	likely_benign	0.1332	benign	-1.419	Destabilizing	0.006	N	0.239	neutral	N	0.458147993	None	None	I
I/W	0.996	likely_pathogenic	0.9966	pathogenic	-1.625	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	I
I/Y	0.9848	likely_pathogenic	0.9869	pathogenic	-1.408	Destabilizing	0.978	D	0.775	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.