TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15743	47452;47453;47454	chr2:178618231;178618230;178618229	chr2:179482958;179482957;179482956
N2AB	14102	42529;42530;42531	chr2:178618231;178618230;178618229	chr2:179482958;179482957;179482956
N2A	13175	39748;39749;39750	chr2:178618231;178618230;178618229	chr2:179482958;179482957;179482956
N2B	6678	20257;20258;20259	chr2:178618231;178618230;178618229	chr2:179482958;179482957;179482956
Novex-1	6803	20632;20633;20634	chr2:178618231;178618230;178618229	chr2:179482958;179482957;179482956
Novex-2	6870	20833;20834;20835	chr2:178618231;178618230;178618229	chr2:179482958;179482957;179482956
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-1
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.288
• 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
P/S	rs757923194	-1.364	0.92	D	0.485	0.262	0.238705975628	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
P/S	rs757923194	-1.364	0.92	D	0.485	0.262	0.238705975628	gnomAD-4.0.0	1.59334E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86234E-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
P/A	0.0775	likely_benign	0.0807	benign	-1.046	Destabilizing	0.959	D	0.487	neutral	N	0.477488422	None	None	N
P/C	0.6449	likely_pathogenic	0.4553	ambiguous	-0.736	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
P/D	0.789	likely_pathogenic	0.734	pathogenic	-0.782	Destabilizing	0.884	D	0.463	neutral	None	None	None	None	N
P/E	0.655	likely_pathogenic	0.6069	pathogenic	-0.87	Destabilizing	0.939	D	0.457	neutral	None	None	None	None	N
P/F	0.5893	likely_pathogenic	0.4768	ambiguous	-1.033	Destabilizing	0.991	D	0.721	prob.delet.	None	None	None	None	N
P/G	0.4602	ambiguous	0.3952	ambiguous	-1.25	Destabilizing	0.939	D	0.544	neutral	None	None	None	None	N
P/H	0.4496	ambiguous	0.3799	ambiguous	-0.712	Destabilizing	0.991	D	0.659	neutral	None	None	None	None	N
P/I	0.4696	ambiguous	0.3871	ambiguous	-0.632	Destabilizing	0.321	N	0.551	neutral	None	None	None	None	N
P/K	0.7525	likely_pathogenic	0.6771	pathogenic	-0.83	Destabilizing	0.939	D	0.46	neutral	None	None	None	None	N
P/L	0.2836	likely_benign	0.2469	benign	-0.632	Destabilizing	0.852	D	0.577	neutral	D	0.617323586	None	None	N
P/M	0.4476	ambiguous	0.3823	ambiguous	-0.476	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
P/N	0.5963	likely_pathogenic	0.5082	ambiguous	-0.512	Destabilizing	0.079	N	0.433	neutral	None	None	None	None	N
P/Q	0.4382	ambiguous	0.396	ambiguous	-0.798	Destabilizing	0.988	D	0.524	neutral	D	0.697251456	None	None	N
P/R	0.6053	likely_pathogenic	0.5413	ambiguous	-0.211	Destabilizing	0.988	D	0.599	neutral	D	0.658400811	None	None	N
P/S	0.2149	likely_benign	0.1865	benign	-0.939	Destabilizing	0.92	D	0.485	neutral	D	0.554389347	None	None	N
P/T	0.1886	likely_benign	0.1568	benign	-0.929	Destabilizing	0.92	D	0.465	neutral	D	0.6197938	None	None	N
P/V	0.3052	likely_benign	0.2536	benign	-0.735	Destabilizing	0.884	D	0.533	neutral	None	None	None	None	N
P/W	0.8023	likely_pathogenic	0.669	pathogenic	-1.086	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
P/Y	0.5925	likely_pathogenic	0.4645	ambiguous	-0.825	Destabilizing	0.997	D	0.723	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.