TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30118	90577;90578;90579	chr2:178552548;178552547;178552546	chr2:179417275;179417274;179417273
N2AB	28477	85654;85655;85656	chr2:178552548;178552547;178552546	chr2:179417275;179417274;179417273
N2A	27550	82873;82874;82875	chr2:178552548;178552547;178552546	chr2:179417275;179417274;179417273
N2B	21053	63382;63383;63384	chr2:178552548;178552547;178552546	chr2:179417275;179417274;179417273
Novex-1	21178	63757;63758;63759	chr2:178552548;178552547;178552546	chr2:179417275;179417274;179417273
Novex-2	21245	63958;63959;63960	chr2:178552548;178552547;178552546	chr2:179417275;179417274;179417273
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-107
• Domain position: 89
• Structural Position: 125
• Q(SASA): 0.5214
• 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
G/R	None	None	0.981	N	0.609	0.356	0.720588202531	gnomAD-4.0.0	2.73687E-06	None	None	None	None	N	None	8.96218E-05	0	None	0	0	None	0	1.7343E-04	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
G/A	0.2965	likely_benign	0.2458	benign	-0.259	Destabilizing	0.022	N	0.304	neutral	N	0.493359432	None	None	N
G/C	0.5846	likely_pathogenic	0.4829	ambiguous	-0.879	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
G/D	0.8644	likely_pathogenic	0.7722	pathogenic	-0.492	Destabilizing	0.971	D	0.622	neutral	None	None	None	None	N
G/E	0.8162	likely_pathogenic	0.7085	pathogenic	-0.613	Destabilizing	0.961	D	0.618	neutral	N	0.451571524	None	None	N
G/F	0.8899	likely_pathogenic	0.8202	pathogenic	-0.783	Destabilizing	0.995	D	0.696	prob.delet.	None	None	None	None	N
G/H	0.9172	likely_pathogenic	0.855	pathogenic	-0.52	Destabilizing	0.999	D	0.659	prob.neutral	None	None	None	None	N
G/I	0.7732	likely_pathogenic	0.6488	pathogenic	-0.238	Destabilizing	0.971	D	0.71	prob.delet.	None	None	None	None	N
G/K	0.9225	likely_pathogenic	0.8712	pathogenic	-0.9	Destabilizing	0.971	D	0.629	neutral	None	None	None	None	N
G/L	0.7951	likely_pathogenic	0.6936	pathogenic	-0.238	Destabilizing	0.971	D	0.615	neutral	None	None	None	None	N
G/M	0.8593	likely_pathogenic	0.7789	pathogenic	-0.466	Destabilizing	0.999	D	0.706	prob.delet.	None	None	None	None	N
G/N	0.8416	likely_pathogenic	0.7744	pathogenic	-0.605	Destabilizing	0.971	D	0.633	neutral	None	None	None	None	N
G/P	0.9437	likely_pathogenic	0.9069	pathogenic	-0.209	Destabilizing	0.985	D	0.62	neutral	None	None	None	None	N
G/Q	0.8554	likely_pathogenic	0.7802	pathogenic	-0.813	Destabilizing	0.985	D	0.675	prob.neutral	None	None	None	None	N
G/R	0.8652	likely_pathogenic	0.7938	pathogenic	-0.507	Destabilizing	0.981	D	0.609	neutral	N	0.498864039	None	None	N
G/S	0.2968	likely_benign	0.2579	benign	-0.785	Destabilizing	0.459	N	0.277	neutral	None	None	None	None	N
G/T	0.5094	ambiguous	0.4093	ambiguous	-0.824	Destabilizing	0.226	N	0.439	neutral	None	None	None	None	N
G/V	0.6705	likely_pathogenic	0.5376	ambiguous	-0.209	Destabilizing	0.926	D	0.611	neutral	N	0.420731329	None	None	N
G/W	0.8681	likely_pathogenic	0.7948	pathogenic	-1.014	Destabilizing	0.998	D	0.622	neutral	N	0.487575206	None	None	N
G/Y	0.8578	likely_pathogenic	0.7798	pathogenic	-0.632	Destabilizing	0.999	D	0.695	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.