TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2643	8152;8153;8154	chr2:178771400;178771399;178771398	chr2:179636127;179636126;179636125
N2AB	2643	8152;8153;8154	chr2:178771400;178771399;178771398	chr2:179636127;179636126;179636125
N2A	2643	8152;8153;8154	chr2:178771400;178771399;178771398	chr2:179636127;179636126;179636125
N2B	2597	8014;8015;8016	chr2:178771400;178771399;178771398	chr2:179636127;179636126;179636125
Novex-1	2597	8014;8015;8016	chr2:178771400;178771399;178771398	chr2:179636127;179636126;179636125
Novex-2	2597	8014;8015;8016	chr2:178771400;178771399;178771398	chr2:179636127;179636126;179636125
Novex-3	2643	8152;8153;8154	chr2:178771400;178771399;178771398	chr2:179636127;179636126;179636125

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-16
• Domain position: 23
• Structural Position: 35
• Q(SASA): 0.1389
• 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
V/F	rs886042338	-1.526	1.0	D	0.832	0.621	0.782848552693	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
V/F	rs886042338	-1.526	1.0	D	0.832	0.621	0.782848552693	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.5937	likely_pathogenic	0.5888	pathogenic	-2.099	Highly Destabilizing	0.999	D	0.591	neutral	D	0.527303492	None	None	N
V/C	0.971	likely_pathogenic	0.9723	pathogenic	-2.163	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
V/D	0.9483	likely_pathogenic	0.9497	pathogenic	-3.475	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.763675296	None	None	N
V/E	0.9029	likely_pathogenic	0.9104	pathogenic	-3.323	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/F	0.711	likely_pathogenic	0.7096	pathogenic	-1.232	Destabilizing	1.0	D	0.832	deleterious	D	0.610564112	None	None	N
V/G	0.7199	likely_pathogenic	0.7087	pathogenic	-2.533	Highly Destabilizing	1.0	D	0.832	deleterious	D	0.763675296	None	None	N
V/H	0.9863	likely_pathogenic	0.9868	pathogenic	-2.178	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/I	0.1293	likely_benign	0.1347	benign	-0.902	Destabilizing	0.997	D	0.529	neutral	D	0.547719177	None	None	N
V/K	0.9635	likely_pathogenic	0.9646	pathogenic	-1.899	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/L	0.5553	ambiguous	0.5569	ambiguous	-0.902	Destabilizing	0.997	D	0.602	neutral	N	0.520659141	None	None	N
V/M	0.5438	ambiguous	0.5613	ambiguous	-1.125	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/N	0.922	likely_pathogenic	0.9278	pathogenic	-2.277	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/P	0.9746	likely_pathogenic	0.9728	pathogenic	-1.277	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/Q	0.9536	likely_pathogenic	0.9565	pathogenic	-2.218	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/R	0.9467	likely_pathogenic	0.9481	pathogenic	-1.572	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/S	0.8256	likely_pathogenic	0.8311	pathogenic	-2.709	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/T	0.5135	ambiguous	0.5191	ambiguous	-2.443	Highly Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
V/W	0.9916	likely_pathogenic	0.9923	pathogenic	-1.768	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/Y	0.9617	likely_pathogenic	0.9631	pathogenic	-1.486	Destabilizing	1.0	D	0.835	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.