TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32200	96823;96824;96825	chr2:178543375;178543374;178543373	chr2:179408102;179408101;179408100
N2AB	30559	91900;91901;91902	chr2:178543375;178543374;178543373	chr2:179408102;179408101;179408100
N2A	29632	89119;89120;89121	chr2:178543375;178543374;178543373	chr2:179408102;179408101;179408100
N2B	23135	69628;69629;69630	chr2:178543375;178543374;178543373	chr2:179408102;179408101;179408100
Novex-1	23260	70003;70004;70005	chr2:178543375;178543374;178543373	chr2:179408102;179408101;179408100
Novex-2	23327	70204;70205;70206	chr2:178543375;178543374;178543373	chr2:179408102;179408101;179408100
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-122
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.2523
• 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/L	None	None	0.999	N	0.565	0.273	0.490631539035	gnomAD-4.0.0	4.10515E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.3967E-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
S/A	0.0907	likely_benign	0.0874	benign	-0.691	Destabilizing	0.57	D	0.367	neutral	N	0.463353451	None	None	N
S/C	0.1183	likely_benign	0.1127	benign	-0.602	Destabilizing	0.636	D	0.281	neutral	None	None	None	None	N
S/D	0.9058	likely_pathogenic	0.915	pathogenic	-0.04	Destabilizing	0.997	D	0.491	neutral	None	None	None	None	N
S/E	0.9021	likely_pathogenic	0.9149	pathogenic	-0.097	Destabilizing	0.998	D	0.48	neutral	None	None	None	None	N
S/F	0.7026	likely_pathogenic	0.6782	pathogenic	-1.04	Destabilizing	1.0	D	0.705	prob.delet.	None	None	None	None	N
S/G	0.1561	likely_benign	0.1739	benign	-0.856	Destabilizing	0.995	D	0.355	neutral	None	None	None	None	N
S/H	0.7762	likely_pathogenic	0.7902	pathogenic	-1.32	Destabilizing	1.0	D	0.475	neutral	None	None	None	None	N
S/I	0.7173	likely_pathogenic	0.6864	pathogenic	-0.368	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
S/K	0.9364	likely_pathogenic	0.9443	pathogenic	-0.681	Destabilizing	1.0	D	0.491	neutral	None	None	None	None	N
S/L	0.336	likely_benign	0.3154	benign	-0.368	Destabilizing	0.999	D	0.565	neutral	N	0.471954291	None	None	N
S/M	0.466	ambiguous	0.4655	ambiguous	-0.104	Destabilizing	1.0	D	0.477	neutral	None	None	None	None	N
S/N	0.5512	ambiguous	0.5862	pathogenic	-0.501	Destabilizing	0.974	D	0.543	neutral	None	None	None	None	N
S/P	0.9359	likely_pathogenic	0.9313	pathogenic	-0.446	Destabilizing	0.999	D	0.554	neutral	N	0.48945983	None	None	N
S/Q	0.7879	likely_pathogenic	0.8154	pathogenic	-0.773	Destabilizing	1.0	D	0.456	neutral	None	None	None	None	N
S/R	0.8686	likely_pathogenic	0.8833	pathogenic	-0.477	Destabilizing	1.0	D	0.559	neutral	None	None	None	None	N
S/T	0.1611	likely_benign	0.1562	benign	-0.623	Destabilizing	0.599	D	0.423	neutral	N	0.519169448	None	None	N
S/V	0.5297	ambiguous	0.5033	ambiguous	-0.446	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
S/W	0.7509	likely_pathogenic	0.7364	pathogenic	-0.949	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
S/Y	0.6049	likely_pathogenic	0.5945	pathogenic	-0.716	Destabilizing	1.0	D	0.707	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.