TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29560	88903;88904;88905	chr2:178554669;178554668;178554667	chr2:179419396;179419395;179419394
N2AB	27919	83980;83981;83982	chr2:178554669;178554668;178554667	chr2:179419396;179419395;179419394
N2A	26992	81199;81200;81201	chr2:178554669;178554668;178554667	chr2:179419396;179419395;179419394
N2B	20495	61708;61709;61710	chr2:178554669;178554668;178554667	chr2:179419396;179419395;179419394
Novex-1	20620	62083;62084;62085	chr2:178554669;178554668;178554667	chr2:179419396;179419395;179419394
Novex-2	20687	62284;62285;62286	chr2:178554669;178554668;178554667	chr2:179419396;179419395;179419394
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: Fn3-103
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.7566
• 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/A	None	None	0.999	N	0.559	0.419	0.381916209588	gnomAD-4.0.0	1.36832E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79884E-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
D/A	0.3943	ambiguous	0.457	ambiguous	-0.161	Destabilizing	0.999	D	0.559	neutral	N	0.471329105	None	None	I
D/C	0.8148	likely_pathogenic	0.85	pathogenic	0.256	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
D/E	0.3489	ambiguous	0.3925	ambiguous	-0.264	Destabilizing	0.981	D	0.384	neutral	N	0.447002706	None	None	I
D/F	0.7974	likely_pathogenic	0.8464	pathogenic	-0.285	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
D/G	0.4626	ambiguous	0.5237	ambiguous	-0.335	Destabilizing	0.998	D	0.587	neutral	N	0.466569391	None	None	I
D/H	0.5467	ambiguous	0.6138	pathogenic	-0.205	Destabilizing	1.0	D	0.623	neutral	N	0.50614701	None	None	I
D/I	0.6628	likely_pathogenic	0.6938	pathogenic	0.241	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
D/K	0.7329	likely_pathogenic	0.7708	pathogenic	0.448	Stabilizing	0.998	D	0.592	neutral	None	None	None	None	I
D/L	0.6819	likely_pathogenic	0.7068	pathogenic	0.241	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	I
D/M	0.8232	likely_pathogenic	0.8429	pathogenic	0.449	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	I
D/N	0.1456	likely_benign	0.1584	benign	0.248	Stabilizing	0.999	D	0.632	neutral	N	0.4956793	None	None	I
D/P	0.9646	likely_pathogenic	0.9667	pathogenic	0.129	Stabilizing	1.0	D	0.658	neutral	None	None	None	None	I
D/Q	0.6104	likely_pathogenic	0.6574	pathogenic	0.267	Stabilizing	0.967	D	0.42	neutral	None	None	None	None	I
D/R	0.7265	likely_pathogenic	0.7744	pathogenic	0.492	Stabilizing	0.999	D	0.66	neutral	None	None	None	None	I
D/S	0.2632	likely_benign	0.2999	benign	0.151	Stabilizing	0.997	D	0.565	neutral	None	None	None	None	I
D/T	0.505	ambiguous	0.5178	ambiguous	0.284	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	I
D/V	0.4419	ambiguous	0.4865	ambiguous	0.129	Stabilizing	0.999	D	0.665	neutral	N	0.469354095	None	None	I
D/W	0.9628	likely_pathogenic	0.9742	pathogenic	-0.225	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
D/Y	0.4616	ambiguous	0.5353	ambiguous	-0.061	Destabilizing	1.0	D	0.657	neutral	N	0.488638684	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.