TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27550	82873;82874;82875	chr2:178563484;178563483;178563482	chr2:179428211;179428210;179428209
N2AB	25909	77950;77951;77952	chr2:178563484;178563483;178563482	chr2:179428211;179428210;179428209
N2A	24982	75169;75170;75171	chr2:178563484;178563483;178563482	chr2:179428211;179428210;179428209
N2B	18485	55678;55679;55680	chr2:178563484;178563483;178563482	chr2:179428211;179428210;179428209
Novex-1	18610	56053;56054;56055	chr2:178563484;178563483;178563482	chr2:179428211;179428210;179428209
Novex-2	18677	56254;56255;56256	chr2:178563484;178563483;178563482	chr2:179428211;179428210;179428209
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-88
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.4966
• 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
A/T	rs778350547	-0.152	1.0	N	0.777	0.385	0.336155897331	gnomAD-2.1.1	4.42E-05	None	None	None	None	I	None	0	2.6087E-04	None	0	0	None	0	None	0	0	3.31126E-04
A/T	rs778350547	-0.152	1.0	N	0.777	0.385	0.336155897331	gnomAD-4.0.0	1.59135E-05	None	None	None	None	I	None	0	1.82932E-04	None	0	0	None	0	0	0	0	6.04961E-05

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
A/C	0.571	likely_pathogenic	0.6631	pathogenic	-0.779	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
A/D	0.922	likely_pathogenic	0.9332	pathogenic	-0.575	Destabilizing	1.0	D	0.867	deleterious	N	0.482168885	None	None	I
A/E	0.8222	likely_pathogenic	0.8635	pathogenic	-0.738	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
A/F	0.5545	ambiguous	0.7003	pathogenic	-0.918	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
A/G	0.3176	likely_benign	0.3429	ambiguous	-0.238	Destabilizing	1.0	D	0.617	neutral	N	0.488636892	None	None	I
A/H	0.8669	likely_pathogenic	0.9144	pathogenic	-0.207	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
A/I	0.3639	ambiguous	0.4728	ambiguous	-0.387	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
A/K	0.9111	likely_pathogenic	0.9396	pathogenic	-0.554	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
A/L	0.4287	ambiguous	0.5031	ambiguous	-0.387	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
A/M	0.4327	ambiguous	0.5553	ambiguous	-0.455	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
A/N	0.7926	likely_pathogenic	0.8465	pathogenic	-0.246	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
A/P	0.9194	likely_pathogenic	0.9391	pathogenic	-0.304	Destabilizing	1.0	D	0.815	deleterious	D	0.538256077	None	None	I
A/Q	0.7752	likely_pathogenic	0.8427	pathogenic	-0.551	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
A/R	0.8006	likely_pathogenic	0.8545	pathogenic	-0.056	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
A/S	0.1859	likely_benign	0.2043	benign	-0.418	Destabilizing	1.0	D	0.618	neutral	N	0.484246027	None	None	I
A/T	0.267	likely_benign	0.2317	benign	-0.509	Destabilizing	1.0	D	0.777	deleterious	N	0.484904364	None	None	I
A/V	0.1544	likely_benign	0.2274	benign	-0.304	Destabilizing	1.0	D	0.713	prob.delet.	N	0.513401056	None	None	I
A/W	0.9271	likely_pathogenic	0.9516	pathogenic	-1.02	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
A/Y	0.819	likely_pathogenic	0.8755	pathogenic	-0.688	Destabilizing	1.0	D	0.879	deleterious	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.