TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30257	90994;90995;90996	chr2:178552131;178552130;178552129	chr2:179416858;179416857;179416856
N2AB	28616	86071;86072;86073	chr2:178552131;178552130;178552129	chr2:179416858;179416857;179416856
N2A	27689	83290;83291;83292	chr2:178552131;178552130;178552129	chr2:179416858;179416857;179416856
N2B	21192	63799;63800;63801	chr2:178552131;178552130;178552129	chr2:179416858;179416857;179416856
Novex-1	21317	64174;64175;64176	chr2:178552131;178552130;178552129	chr2:179416858;179416857;179416856
Novex-2	21384	64375;64376;64377	chr2:178552131;178552130;178552129	chr2:179416858;179416857;179416856
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-108
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.1909
• 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/V	None	None	0.993	N	0.385	0.274	0.620317764101	gnomAD-4.0.0	1.59132E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85822E-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	0.9745	likely_pathogenic	0.9727	pathogenic	-2.261	Highly Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
I/C	0.9785	likely_pathogenic	0.9769	pathogenic	-1.285	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
I/D	0.9953	likely_pathogenic	0.9949	pathogenic	-2.096	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/E	0.9893	likely_pathogenic	0.9877	pathogenic	-2.061	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
I/F	0.8631	likely_pathogenic	0.8624	pathogenic	-1.675	Destabilizing	1.0	D	0.829	deleterious	D	0.536880633	None	None	N
I/G	0.9944	likely_pathogenic	0.9935	pathogenic	-2.641	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
I/H	0.9937	likely_pathogenic	0.9928	pathogenic	-1.909	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
I/K	0.9824	likely_pathogenic	0.9787	pathogenic	-1.659	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/L	0.3864	ambiguous	0.4238	ambiguous	-1.246	Destabilizing	0.993	D	0.405	neutral	N	0.485023403	None	None	N
I/M	0.4137	ambiguous	0.4188	ambiguous	-0.799	Destabilizing	1.0	D	0.804	deleterious	D	0.545998894	None	None	N
I/N	0.9285	likely_pathogenic	0.9123	pathogenic	-1.482	Destabilizing	1.0	D	0.875	deleterious	D	0.558369157	None	None	N
I/P	0.9598	likely_pathogenic	0.9523	pathogenic	-1.557	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
I/Q	0.988	likely_pathogenic	0.9862	pathogenic	-1.655	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
I/R	0.9828	likely_pathogenic	0.9795	pathogenic	-1.0	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/S	0.9779	likely_pathogenic	0.9749	pathogenic	-2.086	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.546252383	None	None	N
I/T	0.9444	likely_pathogenic	0.9396	pathogenic	-1.934	Destabilizing	1.0	D	0.845	deleterious	D	0.534896078	None	None	N
I/V	0.1458	likely_benign	0.1663	benign	-1.557	Destabilizing	0.993	D	0.385	neutral	N	0.488316184	None	None	N
I/W	0.9943	likely_pathogenic	0.9945	pathogenic	-1.825	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/Y	0.975	likely_pathogenic	0.9711	pathogenic	-1.638	Destabilizing	1.0	D	0.862	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.