TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19200	57823;57824;57825	chr2:178595756;178595755;178595754	chr2:179460483;179460482;179460481
N2AB	17559	52900;52901;52902	chr2:178595756;178595755;178595754	chr2:179460483;179460482;179460481
N2A	16632	50119;50120;50121	chr2:178595756;178595755;178595754	chr2:179460483;179460482;179460481
N2B	10135	30628;30629;30630	chr2:178595756;178595755;178595754	chr2:179460483;179460482;179460481
Novex-1	10260	31003;31004;31005	chr2:178595756;178595755;178595754	chr2:179460483;179460482;179460481
Novex-2	10327	31204;31205;31206	chr2:178595756;178595755;178595754	chr2:179460483;179460482;179460481
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-27
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.1593
• 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
S/F	None	None	1.0	N	0.86	0.483	0.571693661435	gnomAD-4.0.0	1.60272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45921E-05	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
S/A	0.1172	likely_benign	0.1186	benign	-0.519	Destabilizing	0.997	D	0.485	neutral	N	0.475645789	None	None	N
S/C	0.1465	likely_benign	0.1488	benign	-0.814	Destabilizing	1.0	D	0.804	deleterious	N	0.485409159	None	None	N
S/D	0.6364	likely_pathogenic	0.6833	pathogenic	-1.843	Destabilizing	0.999	D	0.538	neutral	None	None	None	None	N
S/E	0.7139	likely_pathogenic	0.7504	pathogenic	-1.772	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	N
S/F	0.2543	likely_benign	0.268	benign	-0.713	Destabilizing	1.0	D	0.86	deleterious	N	0.497664064	None	None	N
S/G	0.1501	likely_benign	0.161	benign	-0.791	Destabilizing	0.999	D	0.505	neutral	None	None	None	None	N
S/H	0.4482	ambiguous	0.4735	ambiguous	-1.297	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/I	0.3312	likely_benign	0.348	ambiguous	0.111	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
S/K	0.8555	likely_pathogenic	0.8812	pathogenic	-0.707	Destabilizing	0.999	D	0.528	neutral	None	None	None	None	N
S/L	0.1812	likely_benign	0.1908	benign	0.111	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
S/M	0.236	likely_benign	0.2271	benign	0.259	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
S/N	0.2005	likely_benign	0.1991	benign	-1.179	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
S/P	0.9747	likely_pathogenic	0.985	pathogenic	-0.065	Destabilizing	1.0	D	0.829	deleterious	D	0.529757971	None	None	N
S/Q	0.6406	likely_pathogenic	0.6517	pathogenic	-1.292	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
S/R	0.8186	likely_pathogenic	0.8486	pathogenic	-0.647	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/T	0.0871	likely_benign	0.0886	benign	-0.877	Destabilizing	0.999	D	0.499	neutral	N	0.48997241	None	None	N
S/V	0.3039	likely_benign	0.3115	benign	-0.065	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/W	0.5271	ambiguous	0.5736	pathogenic	-0.903	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/Y	0.2351	likely_benign	0.2567	benign	-0.488	Destabilizing	1.0	D	0.868	deleterious	N	0.477887514	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.