TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32561	97906;97907;97908	chr2:178541396;178541395;178541394	chr2:179406123;179406122;179406121
N2AB	30920	92983;92984;92985	chr2:178541396;178541395;178541394	chr2:179406123;179406122;179406121
N2A	29993	90202;90203;90204	chr2:178541396;178541395;178541394	chr2:179406123;179406122;179406121
N2B	23496	70711;70712;70713	chr2:178541396;178541395;178541394	chr2:179406123;179406122;179406121
Novex-1	23621	71086;71087;71088	chr2:178541396;178541395;178541394	chr2:179406123;179406122;179406121
Novex-2	23688	71287;71288;71289	chr2:178541396;178541395;178541394	chr2:179406123;179406122;179406121
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: Fn3-125
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1625
• 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/P	None	None	0.997	N	0.769	0.506	0.366466682447	gnomAD-4.0.0	1.36989E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99996E-07	0	1.65887E-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
S/A	0.2481	likely_benign	0.2827	benign	-0.689	Destabilizing	0.198	N	0.275	neutral	N	0.393285651	None	None	N
S/C	0.3197	likely_benign	0.3137	benign	-0.441	Destabilizing	1.0	D	0.736	prob.delet.	N	0.446426702	None	None	N
S/D	0.9426	likely_pathogenic	0.9539	pathogenic	-1.126	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
S/E	0.9673	likely_pathogenic	0.9702	pathogenic	-0.937	Destabilizing	0.992	D	0.646	neutral	None	None	None	None	N
S/F	0.9342	likely_pathogenic	0.9512	pathogenic	-0.497	Destabilizing	0.999	D	0.791	deleterious	N	0.43143582	None	None	N
S/G	0.4604	ambiguous	0.5118	ambiguous	-1.111	Destabilizing	0.923	D	0.665	neutral	None	None	None	None	N
S/H	0.94	likely_pathogenic	0.9447	pathogenic	-1.446	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
S/I	0.7069	likely_pathogenic	0.7201	pathogenic	0.382	Stabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
S/K	0.9975	likely_pathogenic	0.9979	pathogenic	-0.301	Destabilizing	0.983	D	0.647	neutral	None	None	None	None	N
S/L	0.6636	likely_pathogenic	0.7001	pathogenic	0.382	Stabilizing	0.983	D	0.757	deleterious	None	None	None	None	N
S/M	0.7637	likely_pathogenic	0.7714	pathogenic	0.384	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
S/N	0.783	likely_pathogenic	0.8025	pathogenic	-0.979	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
S/P	0.9738	likely_pathogenic	0.9791	pathogenic	0.062	Stabilizing	0.997	D	0.769	deleterious	N	0.484040941	None	None	N
S/Q	0.964	likely_pathogenic	0.9665	pathogenic	-0.711	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
S/R	0.9951	likely_pathogenic	0.9962	pathogenic	-0.664	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
S/T	0.1993	likely_benign	0.1963	benign	-0.685	Destabilizing	0.978	D	0.643	neutral	N	0.453891392	None	None	N
S/V	0.5508	ambiguous	0.5518	ambiguous	0.062	Stabilizing	0.983	D	0.751	deleterious	None	None	None	None	N
S/W	0.9464	likely_pathogenic	0.955	pathogenic	-0.752	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/Y	0.8954	likely_pathogenic	0.9135	pathogenic	-0.31	Destabilizing	0.999	D	0.809	deleterious	N	0.494641937	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.