TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6608	20047;20048;20049	chr2:178727756;178727755;178727754	chr2:179592483;179592482;179592481
N2AB	6291	19096;19097;19098	chr2:178727756;178727755;178727754	chr2:179592483;179592482;179592481
N2A	5364	16315;16316;16317	chr2:178727756;178727755;178727754	chr2:179592483;179592482;179592481
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-50
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1769
• 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
F/C	None	None	0.958	N	0.702	0.38	0.743636555992	gnomAD-4.0.0	3.18464E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72145E-06	0	0
F/L	None	None	None	N	0.198	0.127	0.254761474806	gnomAD-4.0.0	6.84402E-07	None	None	None	None	N	None	0	0	None	0	2.52016E-05	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
F/A	0.4276	ambiguous	0.589	pathogenic	-2.921	Highly Destabilizing	0.272	N	0.624	neutral	None	None	None	None	N
F/C	0.2443	likely_benign	0.3589	ambiguous	-1.569	Destabilizing	0.958	D	0.702	prob.neutral	N	0.511009292	None	None	N
F/D	0.7503	likely_pathogenic	0.8053	pathogenic	-2.912	Highly Destabilizing	0.89	D	0.744	deleterious	None	None	None	None	N
F/E	0.643	likely_pathogenic	0.7163	pathogenic	-2.775	Highly Destabilizing	0.726	D	0.73	prob.delet.	None	None	None	None	N
F/G	0.6058	likely_pathogenic	0.7322	pathogenic	-3.299	Highly Destabilizing	0.726	D	0.715	prob.delet.	None	None	None	None	N
F/H	0.3327	likely_benign	0.4063	ambiguous	-1.646	Destabilizing	0.726	D	0.661	neutral	None	None	None	None	N
F/I	0.1713	likely_benign	0.2527	benign	-1.708	Destabilizing	0.124	N	0.511	neutral	N	0.475165949	None	None	N
F/K	0.5043	ambiguous	0.6233	pathogenic	-1.765	Destabilizing	0.726	D	0.726	prob.delet.	None	None	None	None	N
F/L	0.4285	ambiguous	0.6109	pathogenic	-1.708	Destabilizing	None	N	0.198	neutral	N	0.477314465	None	None	N
F/M	0.2758	likely_benign	0.3812	ambiguous	-1.284	Destabilizing	0.396	N	0.563	neutral	None	None	None	None	N
F/N	0.4303	ambiguous	0.5233	ambiguous	-2.004	Highly Destabilizing	0.89	D	0.745	deleterious	None	None	None	None	N
F/P	0.9915	likely_pathogenic	0.9962	pathogenic	-2.119	Highly Destabilizing	0.89	D	0.742	deleterious	None	None	None	None	N
F/Q	0.4255	ambiguous	0.5224	ambiguous	-2.112	Highly Destabilizing	0.89	D	0.741	deleterious	None	None	None	None	N
F/R	0.381	ambiguous	0.4802	ambiguous	-1.044	Destabilizing	0.726	D	0.747	deleterious	None	None	None	None	N
F/S	0.2981	likely_benign	0.3954	ambiguous	-2.672	Highly Destabilizing	0.667	D	0.689	prob.neutral	N	0.50138619	None	None	N
F/T	0.3683	ambiguous	0.5008	ambiguous	-2.442	Highly Destabilizing	0.567	D	0.693	prob.neutral	None	None	None	None	N
F/V	0.1666	likely_benign	0.2582	benign	-2.119	Highly Destabilizing	0.124	N	0.56	neutral	N	0.486522254	None	None	N
F/W	0.2675	likely_benign	0.3238	benign	-0.692	Destabilizing	0.968	D	0.554	neutral	None	None	None	None	N
F/Y	0.1014	likely_benign	0.1184	benign	-1.01	Destabilizing	0.004	N	0.305	neutral	N	0.486395308	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.