TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6279	19060;19061;19062	chr2:178729321;178729320;178729319	chr2:179594048;179594047;179594046
N2AB	5962	18109;18110;18111	chr2:178729321;178729320;178729319	chr2:179594048;179594047;179594046
N2A	5035	15328;15329;15330	chr2:178729321;178729320;178729319	chr2:179594048;179594047;179594046
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-46
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.4914
• Predicted PPI site: I

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
S/R	rs776251068	-0.002	0.984	N	0.625	0.265	0.463328977263	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	8.95E-06	0
S/R	rs776251068	-0.002	0.984	N	0.625	0.265	0.463328977263	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/R	rs776251068	-0.002	0.984	N	0.625	0.265	0.463328977263	gnomAD-4.0.0	3.85259E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.80146E-06	1.34279E-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
S/A	0.1145	likely_benign	0.1101	benign	-0.402	Destabilizing	0.702	D	0.475	neutral	None	None	None	None	I
S/C	0.1906	likely_benign	0.1775	benign	-0.217	Destabilizing	0.999	D	0.654	neutral	N	0.516068851	None	None	I
S/D	0.4413	ambiguous	0.392	ambiguous	-0.024	Destabilizing	0.959	D	0.549	neutral	None	None	None	None	I
S/E	0.4606	ambiguous	0.4154	ambiguous	-0.134	Destabilizing	0.959	D	0.549	neutral	None	None	None	None	I
S/F	0.2053	likely_benign	0.1733	benign	-1.088	Destabilizing	0.952	D	0.701	prob.neutral	None	None	None	None	I
S/G	0.113	likely_benign	0.1158	benign	-0.477	Destabilizing	0.026	N	0.178	neutral	N	0.489708936	None	None	I
S/H	0.2787	likely_benign	0.2701	benign	-1.01	Destabilizing	0.988	D	0.645	neutral	None	None	None	None	I
S/I	0.1478	likely_benign	0.1296	benign	-0.335	Destabilizing	0.984	D	0.709	prob.delet.	N	0.486354801	None	None	I
S/K	0.4619	ambiguous	0.4418	ambiguous	-0.43	Destabilizing	0.959	D	0.549	neutral	None	None	None	None	I
S/L	0.1388	likely_benign	0.1195	benign	-0.335	Destabilizing	0.919	D	0.637	neutral	None	None	None	None	I
S/M	0.2165	likely_benign	0.2099	benign	0.05	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	I
S/N	0.1424	likely_benign	0.1289	benign	-0.121	Destabilizing	0.896	D	0.57	neutral	N	0.520669037	None	None	I
S/P	0.6809	likely_pathogenic	0.6408	pathogenic	-0.332	Destabilizing	0.996	D	0.628	neutral	None	None	None	None	I
S/Q	0.3558	ambiguous	0.3467	ambiguous	-0.44	Destabilizing	0.996	D	0.58	neutral	None	None	None	None	I
S/R	0.3415	ambiguous	0.3171	benign	-0.186	Destabilizing	0.984	D	0.625	neutral	N	0.513857708	None	None	I
S/T	0.0872	likely_benign	0.0865	benign	-0.249	Destabilizing	0.946	D	0.531	neutral	N	0.513145632	None	None	I
S/V	0.1748	likely_benign	0.1642	benign	-0.332	Destabilizing	0.976	D	0.621	neutral	None	None	None	None	I
S/W	0.3719	ambiguous	0.3302	benign	-1.083	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
S/Y	0.1961	likely_benign	0.1657	benign	-0.805	Destabilizing	0.261	N	0.463	neutral	None	None	None	None	I

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.