TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16381	49366;49367;49368	chr2:178614256;178614255;178614254	chr2:179478983;179478982;179478981
N2AB	14740	44443;44444;44445	chr2:178614256;178614255;178614254	chr2:179478983;179478982;179478981
N2A	13813	41662;41663;41664	chr2:178614256;178614255;178614254	chr2:179478983;179478982;179478981
N2B	7316	22171;22172;22173	chr2:178614256;178614255;178614254	chr2:179478983;179478982;179478981
Novex-1	7441	22546;22547;22548	chr2:178614256;178614255;178614254	chr2:179478983;179478982;179478981
Novex-2	7508	22747;22748;22749	chr2:178614256;178614255;178614254	chr2:179478983;179478982;179478981
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-6
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1753
• 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
S/P	None	None	1.0	D	0.777	0.482	0.500994481783	gnomAD-4.0.0	6.84619E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15972E-05	0
S/T	None	None	0.999	N	0.578	0.196	0.358540694251	gnomAD-4.0.0	6.84619E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99792E-07	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
S/A	0.1614	likely_benign	0.142	benign	-0.834	Destabilizing	0.997	D	0.573	neutral	N	0.512274168	None	None	I
S/C	0.1633	likely_benign	0.1353	benign	-0.46	Destabilizing	1.0	D	0.749	deleterious	D	0.567944465	None	None	I
S/D	0.9547	likely_pathogenic	0.9471	pathogenic	-0.461	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
S/E	0.9644	likely_pathogenic	0.9584	pathogenic	-0.461	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	I
S/F	0.8408	likely_pathogenic	0.7988	pathogenic	-1.019	Destabilizing	1.0	D	0.798	deleterious	D	0.698899014	None	None	I
S/G	0.3139	likely_benign	0.2664	benign	-1.09	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	I
S/H	0.9026	likely_pathogenic	0.8762	pathogenic	-1.58	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
S/I	0.8115	likely_pathogenic	0.7665	pathogenic	-0.256	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
S/K	0.992	likely_pathogenic	0.9888	pathogenic	-0.8	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
S/L	0.5646	likely_pathogenic	0.4848	ambiguous	-0.256	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
S/M	0.6336	likely_pathogenic	0.5862	pathogenic	0.153	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
S/N	0.6963	likely_pathogenic	0.6511	pathogenic	-0.758	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	I
S/P	0.9948	likely_pathogenic	0.9917	pathogenic	-0.415	Destabilizing	1.0	D	0.777	deleterious	D	0.734729631	None	None	I
S/Q	0.9313	likely_pathogenic	0.9131	pathogenic	-0.91	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
S/R	0.986	likely_pathogenic	0.979	pathogenic	-0.681	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
S/T	0.2771	likely_benign	0.2563	benign	-0.751	Destabilizing	0.999	D	0.578	neutral	N	0.501212819	None	None	I
S/V	0.6777	likely_pathogenic	0.6231	pathogenic	-0.415	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
S/W	0.9232	likely_pathogenic	0.8965	pathogenic	-0.998	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
S/Y	0.828	likely_pathogenic	0.7767	pathogenic	-0.748	Destabilizing	1.0	D	0.803	deleterious	D	0.698306836	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.