TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18812	56659;56660;56661	chr2:178599359;178599358;178599357	chr2:179464086;179464085;179464084
N2AB	17171	51736;51737;51738	chr2:178599359;178599358;178599357	chr2:179464086;179464085;179464084
N2A	16244	48955;48956;48957	chr2:178599359;178599358;178599357	chr2:179464086;179464085;179464084
N2B	9747	29464;29465;29466	chr2:178599359;178599358;178599357	chr2:179464086;179464085;179464084
Novex-1	9872	29839;29840;29841	chr2:178599359;178599358;178599357	chr2:179464086;179464085;179464084
Novex-2	9939	30040;30041;30042	chr2:178599359;178599358;178599357	chr2:179464086;179464085;179464084
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-24
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.3002
• 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
D/N	None	None	1.0	N	0.665	0.4	0.498259528926	gnomAD-4.0.0	6.88294E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.0172E-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
D/A	0.8579	likely_pathogenic	0.8206	pathogenic	-0.243	Destabilizing	1.0	D	0.694	prob.neutral	N	0.489930793	None	None	I
D/C	0.9706	likely_pathogenic	0.9593	pathogenic	0.2	Stabilizing	1.0	D	0.626	neutral	None	None	None	None	I
D/E	0.8667	likely_pathogenic	0.7998	pathogenic	-0.623	Destabilizing	1.0	D	0.453	neutral	N	0.4851314	None	None	I
D/F	0.9777	likely_pathogenic	0.9725	pathogenic	-0.564	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
D/G	0.8531	likely_pathogenic	0.7922	pathogenic	-0.476	Destabilizing	1.0	D	0.663	neutral	N	0.517949776	None	None	I
D/H	0.898	likely_pathogenic	0.8626	pathogenic	-0.912	Destabilizing	1.0	D	0.623	neutral	N	0.505833002	None	None	I
D/I	0.9547	likely_pathogenic	0.9353	pathogenic	0.327	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
D/K	0.9598	likely_pathogenic	0.9406	pathogenic	0.16	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
D/L	0.953	likely_pathogenic	0.9379	pathogenic	0.327	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
D/M	0.978	likely_pathogenic	0.9678	pathogenic	0.778	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	I
D/N	0.2481	likely_benign	0.2151	benign	-0.08	Destabilizing	1.0	D	0.665	neutral	N	0.514153204	None	None	I
D/P	0.9845	likely_pathogenic	0.9811	pathogenic	0.161	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
D/Q	0.9523	likely_pathogenic	0.9233	pathogenic	-0.038	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/R	0.9595	likely_pathogenic	0.9375	pathogenic	0.022	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
D/S	0.5522	ambiguous	0.4954	ambiguous	-0.202	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
D/T	0.713	likely_pathogenic	0.6376	pathogenic	-0.016	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
D/V	0.902	likely_pathogenic	0.8625	pathogenic	0.161	Stabilizing	1.0	D	0.675	prob.neutral	N	0.508288538	None	None	I
D/W	0.9954	likely_pathogenic	0.994	pathogenic	-0.585	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
D/Y	0.8508	likely_pathogenic	0.808	pathogenic	-0.361	Destabilizing	1.0	D	0.603	neutral	D	0.536054031	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.