TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14886	44881;44882;44883	chr2:178624624;178624623;178624622	chr2:179489351;179489350;179489349
N2AB	13245	39958;39959;39960	chr2:178624624;178624623;178624622	chr2:179489351;179489350;179489349
N2A	12318	37177;37178;37179	chr2:178624624;178624623;178624622	chr2:179489351;179489350;179489349
N2B	5821	17686;17687;17688	chr2:178624624;178624623;178624622	chr2:179489351;179489350;179489349
Novex-1	5946	18061;18062;18063	chr2:178624624;178624623;178624622	chr2:179489351;179489350;179489349
Novex-2	6013	18262;18263;18264	chr2:178624624;178624623;178624622	chr2:179489351;179489350;179489349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-100
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.1545
• 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/Y	rs2058759633	None	0.058	N	0.332	0.189	0.197625483188	gnomAD-4.0.0	8.90043E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.16987E-05	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	0.9547	likely_pathogenic	0.9415	pathogenic	-2.59	Highly Destabilizing	0.86	D	0.634	neutral	None	None	None	None	N
F/C	0.7978	likely_pathogenic	0.7585	pathogenic	-1.468	Destabilizing	0.997	D	0.687	prob.neutral	N	0.470602853	None	None	N
F/D	0.9791	likely_pathogenic	0.9747	pathogenic	-1.779	Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
F/E	0.9646	likely_pathogenic	0.9533	pathogenic	-1.69	Destabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	N
F/G	0.9712	likely_pathogenic	0.964	pathogenic	-2.935	Highly Destabilizing	0.978	D	0.719	prob.delet.	None	None	None	None	N
F/H	0.7737	likely_pathogenic	0.7497	pathogenic	-1.198	Destabilizing	0.978	D	0.631	neutral	None	None	None	None	N
F/I	0.7399	likely_pathogenic	0.681	pathogenic	-1.528	Destabilizing	0.698	D	0.553	neutral	N	0.395879819	None	None	N
F/K	0.9398	likely_pathogenic	0.9233	pathogenic	-1.345	Destabilizing	0.978	D	0.729	prob.delet.	None	None	None	None	N
F/L	0.9442	likely_pathogenic	0.921	pathogenic	-1.528	Destabilizing	0.006	N	0.215	neutral	N	0.345955833	None	None	N
F/M	0.8205	likely_pathogenic	0.7683	pathogenic	-1.231	Destabilizing	0.956	D	0.578	neutral	None	None	None	None	N
F/N	0.9008	likely_pathogenic	0.8844	pathogenic	-1.368	Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.88	Destabilizing	0.993	D	0.742	deleterious	None	None	None	None	N
F/Q	0.9112	likely_pathogenic	0.8875	pathogenic	-1.542	Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
F/R	0.88	likely_pathogenic	0.8466	pathogenic	-0.596	Destabilizing	0.978	D	0.742	deleterious	None	None	None	None	N
F/S	0.8916	likely_pathogenic	0.8574	pathogenic	-2.18	Highly Destabilizing	0.97	D	0.685	prob.neutral	N	0.351150983	None	None	N
F/T	0.9275	likely_pathogenic	0.9046	pathogenic	-1.997	Destabilizing	0.956	D	0.689	prob.neutral	None	None	None	None	N
F/V	0.7563	likely_pathogenic	0.6946	pathogenic	-1.88	Destabilizing	0.698	D	0.605	neutral	N	0.41655305	None	None	N
F/W	0.6255	likely_pathogenic	0.596	pathogenic	-0.629	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	N
F/Y	0.1663	likely_benign	0.1614	benign	-0.832	Destabilizing	0.058	N	0.332	neutral	N	0.345101491	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.