TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25662	77209;77210;77211	chr2:178569148;178569147;178569146	chr2:179433875;179433874;179433873
N2AB	24021	72286;72287;72288	chr2:178569148;178569147;178569146	chr2:179433875;179433874;179433873
N2A	23094	69505;69506;69507	chr2:178569148;178569147;178569146	chr2:179433875;179433874;179433873
N2B	16597	50014;50015;50016	chr2:178569148;178569147;178569146	chr2:179433875;179433874;179433873
Novex-1	16722	50389;50390;50391	chr2:178569148;178569147;178569146	chr2:179433875;179433874;179433873
Novex-2	16789	50590;50591;50592	chr2:178569148;178569147;178569146	chr2:179433875;179433874;179433873
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-74
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.0947
• 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
I/N	None	None	0.939	D	0.838	0.534	0.858602885114	gnomAD-4.0.0	6.84385E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99641E-07	0	0
I/T	None	None	0.684	N	0.78	0.492	0.677526534183	gnomAD-4.0.0	6.84385E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16017E-05	0
I/V	None	None	0.003	N	0.195	0.078	0.44711355012	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86E-06	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
I/A	0.5043	ambiguous	0.5382	ambiguous	-2.509	Highly Destabilizing	0.373	N	0.731	prob.delet.	None	None	None	None	N
I/C	0.8468	likely_pathogenic	0.8602	pathogenic	-1.805	Destabilizing	0.996	D	0.79	deleterious	None	None	None	None	N
I/D	0.99	likely_pathogenic	0.9899	pathogenic	-3.124	Highly Destabilizing	0.984	D	0.833	deleterious	None	None	None	None	N
I/E	0.9753	likely_pathogenic	0.9747	pathogenic	-2.818	Highly Destabilizing	0.953	D	0.803	deleterious	None	None	None	None	N
I/F	0.3814	ambiguous	0.4189	ambiguous	-1.516	Destabilizing	0.884	D	0.767	deleterious	N	0.478801524	None	None	N
I/G	0.9421	likely_pathogenic	0.9493	pathogenic	-3.127	Highly Destabilizing	0.953	D	0.798	deleterious	None	None	None	None	N
I/H	0.9756	likely_pathogenic	0.9766	pathogenic	-2.811	Highly Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	N
I/K	0.9704	likely_pathogenic	0.9688	pathogenic	-1.968	Destabilizing	0.91	D	0.799	deleterious	None	None	None	None	N
I/L	0.2032	likely_benign	0.2098	benign	-0.681	Destabilizing	0.063	N	0.443	neutral	N	0.505912149	None	None	N
I/M	0.154	likely_benign	0.163	benign	-0.734	Destabilizing	0.332	N	0.491	neutral	D	0.522913754	None	None	N
I/N	0.9128	likely_pathogenic	0.907	pathogenic	-2.578	Highly Destabilizing	0.939	D	0.838	deleterious	D	0.523420733	None	None	N
I/P	0.9611	likely_pathogenic	0.9644	pathogenic	-1.276	Destabilizing	0.984	D	0.837	deleterious	None	None	None	None	N
I/Q	0.9626	likely_pathogenic	0.963	pathogenic	-2.272	Highly Destabilizing	0.953	D	0.841	deleterious	None	None	None	None	N
I/R	0.9543	likely_pathogenic	0.9542	pathogenic	-1.967	Destabilizing	0.953	D	0.836	deleterious	None	None	None	None	N
I/S	0.7946	likely_pathogenic	0.8046	pathogenic	-3.224	Highly Destabilizing	0.684	D	0.782	deleterious	N	0.507772013	None	None	N
I/T	0.4174	ambiguous	0.4325	ambiguous	-2.746	Highly Destabilizing	0.684	D	0.78	deleterious	N	0.505062988	None	None	N
I/V	0.0762	likely_benign	0.0778	benign	-1.276	Destabilizing	0.003	N	0.195	neutral	N	0.404249219	None	None	N
I/W	0.9665	likely_pathogenic	0.9679	pathogenic	-1.978	Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	N
I/Y	0.9039	likely_pathogenic	0.9086	pathogenic	-1.654	Destabilizing	0.953	D	0.803	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.