TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5549	16870;16871;16872	chr2:178732324;178732323;178732322	chr2:179597051;179597050;179597049
N2AB	5232	15919;15920;15921	chr2:178732324;178732323;178732322	chr2:179597051;179597050;179597049
N2A	4305	13138;13139;13140	chr2:178732324;178732323;178732322	chr2:179597051;179597050;179597049
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-39
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2226
• 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
L/F	None	None	0.64	N	0.353	0.244	0.270447802918	gnomAD-4.0.0	1.61318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45934E-05	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
L/A	0.4788	ambiguous	0.4206	ambiguous	-2.265	Highly Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
L/C	0.7868	likely_pathogenic	0.7808	pathogenic	-1.574	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9679	likely_pathogenic	0.9609	pathogenic	-1.872	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/E	0.8591	likely_pathogenic	0.8377	pathogenic	-1.772	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/F	0.4635	ambiguous	0.4354	ambiguous	-1.523	Destabilizing	0.64	D	0.353	neutral	N	0.487918287	None	None	N
L/G	0.8239	likely_pathogenic	0.7968	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
L/H	0.8232	likely_pathogenic	0.7982	pathogenic	-1.97	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/I	0.1714	likely_benign	0.161	benign	-1.056	Destabilizing	0.996	D	0.539	neutral	N	0.469622995	None	None	N
L/K	0.8513	likely_pathogenic	0.8232	pathogenic	-1.538	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/M	0.1844	likely_benign	0.1738	benign	-0.883	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
L/N	0.8624	likely_pathogenic	0.8478	pathogenic	-1.516	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/P	0.2626	likely_benign	0.1785	benign	-1.433	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/Q	0.6603	likely_pathogenic	0.6126	pathogenic	-1.583	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/R	0.7581	likely_pathogenic	0.7128	pathogenic	-1.067	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
L/S	0.7741	likely_pathogenic	0.7434	pathogenic	-2.266	Highly Destabilizing	1.0	D	0.765	deleterious	N	0.490805123	None	None	N
L/T	0.4975	ambiguous	0.4483	ambiguous	-2.032	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/V	0.1837	likely_benign	0.1751	benign	-1.433	Destabilizing	0.996	D	0.551	neutral	N	0.463546608	None	None	N
L/W	0.745	likely_pathogenic	0.6823	pathogenic	-1.697	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/Y	0.864	likely_pathogenic	0.8385	pathogenic	-1.459	Destabilizing	0.998	D	0.793	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.