TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33000	99223;99224;99225	chr2:178538831;178538830;178538829	chr2:179403558;179403557;179403556
N2AB	31359	94300;94301;94302	chr2:178538831;178538830;178538829	chr2:179403558;179403557;179403556
N2A	30432	91519;91520;91521	chr2:178538831;178538830;178538829	chr2:179403558;179403557;179403556
N2B	23935	72028;72029;72030	chr2:178538831;178538830;178538829	chr2:179403558;179403557;179403556
Novex-1	24060	72403;72404;72405	chr2:178538831;178538830;178538829	chr2:179403558;179403557;179403556
Novex-2	24127	72604;72605;72606	chr2:178538831;178538830;178538829	chr2:179403558;179403557;179403556
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: Fn3-129
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.317
• 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
S/R	None	None	0.999	D	0.582	0.478	0.456552270603	gnomAD-4.0.0	6.88325E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03122E-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
S/A	0.1519	likely_benign	0.1532	benign	-0.397	Destabilizing	0.923	D	0.546	neutral	None	None	None	None	N
S/C	0.2393	likely_benign	0.201	benign	-0.297	Destabilizing	1.0	D	0.619	neutral	D	0.540149543	None	None	N
S/D	0.8464	likely_pathogenic	0.8034	pathogenic	-0.165	Destabilizing	0.992	D	0.57	neutral	None	None	None	None	N
S/E	0.8968	likely_pathogenic	0.8827	pathogenic	-0.224	Destabilizing	0.997	D	0.569	neutral	None	None	None	None	N
S/F	0.6557	likely_pathogenic	0.6016	pathogenic	-0.733	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
S/G	0.136	likely_benign	0.1232	benign	-0.584	Destabilizing	0.054	N	0.346	neutral	N	0.515580143	None	None	N
S/H	0.8272	likely_pathogenic	0.7887	pathogenic	-1.16	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
S/I	0.6323	likely_pathogenic	0.5714	pathogenic	-0.022	Destabilizing	0.999	D	0.67	neutral	D	0.539896054	None	None	N
S/K	0.9717	likely_pathogenic	0.9598	pathogenic	-0.707	Destabilizing	0.992	D	0.568	neutral	None	None	None	None	N
S/L	0.3153	likely_benign	0.286	benign	-0.022	Destabilizing	0.998	D	0.612	neutral	None	None	None	None	N
S/M	0.5033	ambiguous	0.4868	ambiguous	0.234	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
S/N	0.4781	ambiguous	0.4347	ambiguous	-0.441	Destabilizing	0.989	D	0.573	neutral	D	0.538628606	None	None	N
S/P	0.8715	likely_pathogenic	0.8554	pathogenic	-0.115	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
S/Q	0.8678	likely_pathogenic	0.8544	pathogenic	-0.669	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
S/R	0.95	likely_pathogenic	0.9289	pathogenic	-0.532	Destabilizing	0.999	D	0.582	neutral	D	0.527361206	None	None	N
S/T	0.1828	likely_benign	0.177	benign	-0.48	Destabilizing	0.989	D	0.523	neutral	N	0.500774255	None	None	N
S/V	0.5561	ambiguous	0.5315	ambiguous	-0.115	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
S/W	0.8208	likely_pathogenic	0.7697	pathogenic	-0.74	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
S/Y	0.6772	likely_pathogenic	0.6044	pathogenic	-0.482	Destabilizing	0.999	D	0.693	prob.neutral	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.