TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25998	78217;78218;78219	chr2:178568140;178568139;178568138	chr2:179432867;179432866;179432865
N2AB	24357	73294;73295;73296	chr2:178568140;178568139;178568138	chr2:179432867;179432866;179432865
N2A	23430	70513;70514;70515	chr2:178568140;178568139;178568138	chr2:179432867;179432866;179432865
N2B	16933	51022;51023;51024	chr2:178568140;178568139;178568138	chr2:179432867;179432866;179432865
Novex-1	17058	51397;51398;51399	chr2:178568140;178568139;178568138	chr2:179432867;179432866;179432865
Novex-2	17125	51598;51599;51600	chr2:178568140;178568139;178568138	chr2:179432867;179432866;179432865
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: Fn3-77
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3217
• 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/L	None	None	0.999	N	0.535	0.443	0.243398259712	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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	0.4609	ambiguous	0.5599	ambiguous	-2.2	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
F/C	0.3072	likely_benign	0.3541	ambiguous	-0.768	Destabilizing	1.0	D	0.858	deleterious	N	0.489985479	None	None	N
F/D	0.7844	likely_pathogenic	0.8455	pathogenic	-1.209	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
F/E	0.7551	likely_pathogenic	0.8158	pathogenic	-1.135	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
F/G	0.7794	likely_pathogenic	0.841	pathogenic	-2.523	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
F/H	0.4526	ambiguous	0.5019	ambiguous	-0.803	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
F/I	0.1873	likely_benign	0.2149	benign	-1.224	Destabilizing	1.0	D	0.727	prob.delet.	N	0.446271987	None	None	N
F/K	0.7084	likely_pathogenic	0.7746	pathogenic	-1.085	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
F/L	0.7777	likely_pathogenic	0.8255	pathogenic	-1.224	Destabilizing	0.999	D	0.535	neutral	N	0.457219699	None	None	N
F/M	0.4296	ambiguous	0.4849	ambiguous	-0.736	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
F/N	0.5771	likely_pathogenic	0.6604	pathogenic	-1.1	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
F/P	0.9936	likely_pathogenic	0.9965	pathogenic	-1.544	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
F/Q	0.6186	likely_pathogenic	0.6879	pathogenic	-1.227	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
F/R	0.6137	likely_pathogenic	0.6809	pathogenic	-0.381	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
F/S	0.3074	likely_benign	0.3958	ambiguous	-1.812	Destabilizing	1.0	D	0.835	deleterious	N	0.441535384	None	None	N
F/T	0.3456	ambiguous	0.4249	ambiguous	-1.651	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
F/V	0.1701	likely_benign	0.1938	benign	-1.544	Destabilizing	1.0	D	0.795	deleterious	N	0.422683051	None	None	N
F/W	0.4629	ambiguous	0.4763	ambiguous	-0.484	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
F/Y	0.1551	likely_benign	0.1574	benign	-0.682	Destabilizing	0.999	D	0.493	neutral	N	0.415911794	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.