TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21746	65461;65462;65463	chr2:178584315;178584314;178584313	chr2:179449042;179449041;179449040
N2AB	20105	60538;60539;60540	chr2:178584315;178584314;178584313	chr2:179449042;179449041;179449040
N2A	19178	57757;57758;57759	chr2:178584315;178584314;178584313	chr2:179449042;179449041;179449040
N2B	12681	38266;38267;38268	chr2:178584315;178584314;178584313	chr2:179449042;179449041;179449040
Novex-1	12806	38641;38642;38643	chr2:178584315;178584314;178584313	chr2:179449042;179449041;179449040
Novex-2	12873	38842;38843;38844	chr2:178584315;178584314;178584313	chr2:179449042;179449041;179449040
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-45
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1375
• 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/R	None	None	0.999	D	0.84	0.61	0.550545596621	gnomAD-4.0.0	8.16716E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.17925E-05	1.4741E-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	0.4394	ambiguous	0.3724	ambiguous	-0.874	Destabilizing	0.964	D	0.751	deleterious	None	None	None	None	N
S/C	0.3804	ambiguous	0.3217	benign	-0.744	Destabilizing	0.135	N	0.671	neutral	N	0.516201117	None	None	N
S/D	0.9926	likely_pathogenic	0.9877	pathogenic	-1.587	Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
S/E	0.9946	likely_pathogenic	0.9925	pathogenic	-1.408	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
S/F	0.9926	likely_pathogenic	0.9901	pathogenic	-0.484	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
S/G	0.391	ambiguous	0.2513	benign	-1.261	Destabilizing	0.99	D	0.815	deleterious	N	0.516984358	None	None	N
S/H	0.9891	likely_pathogenic	0.9849	pathogenic	-1.554	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
S/I	0.9803	likely_pathogenic	0.9728	pathogenic	0.107	Stabilizing	0.997	D	0.884	deleterious	D	0.550092222	None	None	N
S/K	0.9991	likely_pathogenic	0.9985	pathogenic	-0.66	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
S/L	0.9136	likely_pathogenic	0.8829	pathogenic	0.107	Stabilizing	0.985	D	0.877	deleterious	None	None	None	None	N
S/M	0.9472	likely_pathogenic	0.9394	pathogenic	-0.041	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/N	0.9621	likely_pathogenic	0.9361	pathogenic	-1.229	Destabilizing	0.999	D	0.857	deleterious	D	0.549838733	None	None	N
S/P	0.9937	likely_pathogenic	0.9919	pathogenic	-0.186	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
S/Q	0.9894	likely_pathogenic	0.9855	pathogenic	-0.998	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
S/R	0.9979	likely_pathogenic	0.996	pathogenic	-0.951	Destabilizing	0.999	D	0.84	deleterious	D	0.537721959	None	None	N
S/T	0.5059	ambiguous	0.4985	ambiguous	-0.907	Destabilizing	0.99	D	0.811	deleterious	N	0.505170299	None	None	N
S/V	0.9437	likely_pathogenic	0.9271	pathogenic	-0.186	Destabilizing	0.996	D	0.875	deleterious	None	None	None	None	N
S/W	0.9939	likely_pathogenic	0.9918	pathogenic	-0.763	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
S/Y	0.9907	likely_pathogenic	0.9868	pathogenic	-0.355	Destabilizing	0.999	D	0.891	deleterious	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.