TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30957	93094;93095;93096	chr2:178548757;178548756;178548755	chr2:179413484;179413483;179413482
N2AB	29316	88171;88172;88173	chr2:178548757;178548756;178548755	chr2:179413484;179413483;179413482
N2A	28389	85390;85391;85392	chr2:178548757;178548756;178548755	chr2:179413484;179413483;179413482
N2B	21892	65899;65900;65901	chr2:178548757;178548756;178548755	chr2:179413484;179413483;179413482
Novex-1	22017	66274;66275;66276	chr2:178548757;178548756;178548755	chr2:179413484;179413483;179413482
Novex-2	22084	66475;66476;66477	chr2:178548757;178548756;178548755	chr2:179413484;179413483;179413482
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-150
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.3063
• 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
A/V	None	None	1.0	N	0.681	0.364	0.406120066682	gnomAD-4.0.0	6.84339E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99465E-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
A/C	0.589	likely_pathogenic	0.5738	pathogenic	-0.748	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
A/D	0.9564	likely_pathogenic	0.95	pathogenic	-1.158	Destabilizing	1.0	D	0.875	deleterious	N	0.498645704	None	None	N
A/E	0.9215	likely_pathogenic	0.9124	pathogenic	-1.105	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/F	0.8285	likely_pathogenic	0.8067	pathogenic	-0.706	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/G	0.3109	likely_benign	0.3023	benign	-1.141	Destabilizing	1.0	D	0.61	neutral	D	0.532462111	None	None	N
A/H	0.9517	likely_pathogenic	0.94	pathogenic	-1.462	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
A/I	0.3767	ambiguous	0.3732	ambiguous	0.059	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
A/K	0.9642	likely_pathogenic	0.9581	pathogenic	-1.012	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
A/L	0.4658	ambiguous	0.4514	ambiguous	0.059	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/M	0.5392	ambiguous	0.5147	ambiguous	-0.009	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
A/N	0.8888	likely_pathogenic	0.8704	pathogenic	-0.86	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/P	0.5323	ambiguous	0.5364	ambiguous	-0.178	Destabilizing	1.0	D	0.81	deleterious	D	0.532462111	None	None	N
A/Q	0.9135	likely_pathogenic	0.8976	pathogenic	-0.876	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/R	0.9356	likely_pathogenic	0.9257	pathogenic	-0.891	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
A/S	0.2158	likely_benign	0.201	benign	-1.279	Destabilizing	1.0	D	0.617	neutral	N	0.513433633	None	None	N
A/T	0.1922	likely_benign	0.18	benign	-1.112	Destabilizing	1.0	D	0.762	deleterious	N	0.509219892	None	None	N
A/V	0.1578	likely_benign	0.1531	benign	-0.178	Destabilizing	1.0	D	0.681	prob.neutral	N	0.378198768	None	None	N
A/W	0.9749	likely_pathogenic	0.9714	pathogenic	-1.229	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
A/Y	0.9309	likely_pathogenic	0.9191	pathogenic	-0.722	Destabilizing	1.0	D	0.887	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.