TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24124	72595;72596;72597	chr2:178573762;178573761;178573760	chr2:179438489;179438488;179438487
N2AB	22483	67672;67673;67674	chr2:178573762;178573761;178573760	chr2:179438489;179438488;179438487
N2A	21556	64891;64892;64893	chr2:178573762;178573761;178573760	chr2:179438489;179438488;179438487
N2B	15059	45400;45401;45402	chr2:178573762;178573761;178573760	chr2:179438489;179438488;179438487
Novex-1	15184	45775;45776;45777	chr2:178573762;178573761;178573760	chr2:179438489;179438488;179438487
Novex-2	15251	45976;45977;45978	chr2:178573762;178573761;178573760	chr2:179438489;179438488;179438487
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-63
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2366
• 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
G/C	None	None	1.0	D	0.788	0.478	0.720684183395	gnomAD-4.0.0	1.6314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92319E-06	0	0
G/D	rs972618040	None	1.0	N	0.858	0.41	0.405700215632	gnomAD-4.0.0	6.92864E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06638E-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
G/A	0.434	ambiguous	0.433	ambiguous	-0.86	Destabilizing	1.0	D	0.715	prob.delet.	N	0.517590474	None	None	N
G/C	0.686	likely_pathogenic	0.6735	pathogenic	-1.222	Destabilizing	1.0	D	0.788	deleterious	D	0.542077511	None	None	N
G/D	0.8895	likely_pathogenic	0.8708	pathogenic	-2.038	Highly Destabilizing	1.0	D	0.858	deleterious	N	0.483113029	None	None	N
G/E	0.8884	likely_pathogenic	0.8604	pathogenic	-2.095	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
G/F	0.9389	likely_pathogenic	0.9319	pathogenic	-1.272	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/H	0.9355	likely_pathogenic	0.9261	pathogenic	-1.346	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/I	0.904	likely_pathogenic	0.8854	pathogenic	-0.52	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/K	0.9321	likely_pathogenic	0.9172	pathogenic	-1.332	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/L	0.8429	likely_pathogenic	0.8441	pathogenic	-0.52	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/M	0.9042	likely_pathogenic	0.9002	pathogenic	-0.449	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/N	0.8503	likely_pathogenic	0.8566	pathogenic	-1.147	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/P	0.9929	likely_pathogenic	0.9911	pathogenic	-0.596	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
G/Q	0.8748	likely_pathogenic	0.8615	pathogenic	-1.405	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/R	0.8807	likely_pathogenic	0.8575	pathogenic	-0.966	Destabilizing	1.0	D	0.859	deleterious	N	0.511349503	None	None	N
G/S	0.3	likely_benign	0.3203	benign	-1.313	Destabilizing	1.0	D	0.757	deleterious	N	0.480880849	None	None	N
G/T	0.6942	likely_pathogenic	0.7096	pathogenic	-1.31	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/V	0.834	likely_pathogenic	0.81	pathogenic	-0.596	Destabilizing	1.0	D	0.867	deleterious	D	0.530467716	None	None	N
G/W	0.934	likely_pathogenic	0.9202	pathogenic	-1.599	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
G/Y	0.933	likely_pathogenic	0.9201	pathogenic	-1.205	Destabilizing	1.0	D	0.853	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.