TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24229	72910;72911;72912	chr2:178573447;178573446;178573445	chr2:179438174;179438173;179438172
N2AB	22588	67987;67988;67989	chr2:178573447;178573446;178573445	chr2:179438174;179438173;179438172
N2A	21661	65206;65207;65208	chr2:178573447;178573446;178573445	chr2:179438174;179438173;179438172
N2B	15164	45715;45716;45717	chr2:178573447;178573446;178573445	chr2:179438174;179438173;179438172
Novex-1	15289	46090;46091;46092	chr2:178573447;178573446;178573445	chr2:179438174;179438173;179438172
Novex-2	15356	46291;46292;46293	chr2:178573447;178573446;178573445	chr2:179438174;179438173;179438172
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-64
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1338
• 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
P/R	rs1708954278	None	0.997	D	0.797	0.433	0.693129305553	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	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
P/A	0.3392	likely_benign	0.3025	benign	-2.037	Highly Destabilizing	0.977	D	0.743	deleterious	N	0.503057844	None	None	N
P/C	0.814	likely_pathogenic	0.7582	pathogenic	-1.866	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/D	0.9956	likely_pathogenic	0.9937	pathogenic	-3.023	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
P/E	0.9813	likely_pathogenic	0.9721	pathogenic	-2.822	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
P/F	0.9632	likely_pathogenic	0.9563	pathogenic	-1.109	Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
P/G	0.9379	likely_pathogenic	0.9231	pathogenic	-2.527	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
P/H	0.9711	likely_pathogenic	0.9564	pathogenic	-2.295	Highly Destabilizing	1.0	D	0.83	deleterious	D	0.546369925	None	None	N
P/I	0.3975	ambiguous	0.352	ambiguous	-0.671	Destabilizing	0.99	D	0.804	deleterious	None	None	None	None	N
P/K	0.9862	likely_pathogenic	0.9783	pathogenic	-1.63	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
P/L	0.2776	likely_benign	0.233	benign	-0.671	Destabilizing	0.235	N	0.735	prob.delet.	N	0.477565181	None	None	N
P/M	0.6825	likely_pathogenic	0.6353	pathogenic	-1.013	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
P/N	0.9865	likely_pathogenic	0.9783	pathogenic	-1.979	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
P/Q	0.9563	likely_pathogenic	0.9309	pathogenic	-1.848	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
P/R	0.9714	likely_pathogenic	0.9557	pathogenic	-1.486	Destabilizing	0.997	D	0.797	deleterious	D	0.546369925	None	None	N
P/S	0.869	likely_pathogenic	0.8249	pathogenic	-2.493	Highly Destabilizing	0.997	D	0.726	prob.delet.	D	0.528012181	None	None	N
P/T	0.5293	ambiguous	0.4322	ambiguous	-2.164	Highly Destabilizing	0.997	D	0.721	prob.delet.	D	0.534506641	None	None	N
P/V	0.266	likely_benign	0.2314	benign	-1.102	Destabilizing	0.99	D	0.771	deleterious	None	None	None	None	N
P/W	0.9936	likely_pathogenic	0.9904	pathogenic	-1.64	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/Y	0.9862	likely_pathogenic	0.9803	pathogenic	-1.295	Destabilizing	0.999	D	0.863	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.