TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24745	74458;74459;74460	chr2:178571899;178571898;178571897	chr2:179436626;179436625;179436624
N2AB	23104	69535;69536;69537	chr2:178571899;178571898;178571897	chr2:179436626;179436625;179436624
N2A	22177	66754;66755;66756	chr2:178571899;178571898;178571897	chr2:179436626;179436625;179436624
N2B	15680	47263;47264;47265	chr2:178571899;178571898;178571897	chr2:179436626;179436625;179436624
Novex-1	15805	47638;47639;47640	chr2:178571899;178571898;178571897	chr2:179436626;179436625;179436624
Novex-2	15872	47839;47840;47841	chr2:178571899;178571898;178571897	chr2:179436626;179436625;179436624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-133
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.0983
• 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
P/S	rs1708317889	None	0.956	D	0.589	0.523	0.483521307902	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	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
P/A	0.2133	likely_benign	0.1978	benign	-1.931	Destabilizing	0.198	N	0.375	neutral	N	0.513989526	None	None	N
P/C	0.8635	likely_pathogenic	0.8766	pathogenic	-1.698	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/D	0.9957	likely_pathogenic	0.9962	pathogenic	-2.314	Highly Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
P/E	0.9842	likely_pathogenic	0.987	pathogenic	-2.204	Highly Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
P/F	0.9919	likely_pathogenic	0.9921	pathogenic	-1.343	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
P/G	0.8819	likely_pathogenic	0.8753	pathogenic	-2.356	Highly Destabilizing	0.967	D	0.59	neutral	None	None	None	None	N
P/H	0.9793	likely_pathogenic	0.9815	pathogenic	-1.952	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
P/I	0.8719	likely_pathogenic	0.8737	pathogenic	-0.797	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
P/K	0.9889	likely_pathogenic	0.9902	pathogenic	-1.484	Destabilizing	0.995	D	0.682	prob.neutral	None	None	None	None	N
P/L	0.7455	likely_pathogenic	0.7378	pathogenic	-0.797	Destabilizing	0.978	D	0.709	prob.delet.	D	0.548459608	None	None	N
P/M	0.9337	likely_pathogenic	0.9337	pathogenic	-0.903	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
P/N	0.9892	likely_pathogenic	0.9905	pathogenic	-1.575	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
P/Q	0.9637	likely_pathogenic	0.9669	pathogenic	-1.619	Destabilizing	0.999	D	0.674	neutral	D	0.575899614	None	None	N
P/R	0.9701	likely_pathogenic	0.9718	pathogenic	-1.159	Destabilizing	0.997	D	0.709	prob.delet.	D	0.575899614	None	None	N
P/S	0.7912	likely_pathogenic	0.7864	pathogenic	-2.174	Highly Destabilizing	0.956	D	0.589	neutral	D	0.545767491	None	None	N
P/T	0.738	likely_pathogenic	0.7535	pathogenic	-1.938	Destabilizing	0.978	D	0.663	neutral	D	0.55251544	None	None	N
P/V	0.6931	likely_pathogenic	0.6907	pathogenic	-1.145	Destabilizing	0.983	D	0.658	neutral	None	None	None	None	N
P/W	0.9977	likely_pathogenic	0.9978	pathogenic	-1.672	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
P/Y	0.9931	likely_pathogenic	0.9935	pathogenic	-1.331	Destabilizing	0.999	D	0.763	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.