TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25221	75886;75887;75888	chr2:178570471;178570470;178570469	chr2:179435198;179435197;179435196
N2AB	23580	70963;70964;70965	chr2:178570471;178570470;178570469	chr2:179435198;179435197;179435196
N2A	22653	68182;68183;68184	chr2:178570471;178570470;178570469	chr2:179435198;179435197;179435196
N2B	16156	48691;48692;48693	chr2:178570471;178570470;178570469	chr2:179435198;179435197;179435196
Novex-1	16281	49066;49067;49068	chr2:178570471;178570470;178570469	chr2:179435198;179435197;179435196
Novex-2	16348	49267;49268;49269	chr2:178570471;178570470;178570469	chr2:179435198;179435197;179435196
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-71
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.3063
• 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
K/R	rs745540831	-0.703	0.999	N	0.61	0.204	0.344251166708	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14916E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs745540831	-0.703	0.999	N	0.61	0.204	0.344251166708	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
K/R	rs745540831	-0.703	0.999	N	0.61	0.204	0.344251166708	gnomAD-4.0.0	2.03018E-06	None	None	None	None	N	None	3.49675E-05	0	None	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
K/A	0.7438	likely_pathogenic	0.8177	pathogenic	-0.667	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
K/C	0.7982	likely_pathogenic	0.8647	pathogenic	-0.963	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
K/D	0.8901	likely_pathogenic	0.9199	pathogenic	-0.842	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/E	0.6817	likely_pathogenic	0.743	pathogenic	-0.736	Destabilizing	0.999	D	0.609	neutral	N	0.503645422	None	None	N
K/F	0.8966	likely_pathogenic	0.9325	pathogenic	-0.503	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/G	0.7519	likely_pathogenic	0.8189	pathogenic	-1.021	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
K/H	0.4154	ambiguous	0.4891	ambiguous	-1.414	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
K/I	0.7249	likely_pathogenic	0.7983	pathogenic	0.25	Stabilizing	1.0	D	0.859	deleterious	N	0.493373833	None	None	N
K/L	0.7218	likely_pathogenic	0.7934	pathogenic	0.25	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
K/M	0.4743	ambiguous	0.5647	pathogenic	0.21	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/N	0.7118	likely_pathogenic	0.7809	pathogenic	-0.867	Destabilizing	1.0	D	0.718	prob.delet.	N	0.496066089	None	None	N
K/P	0.9892	likely_pathogenic	0.994	pathogenic	-0.026	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/Q	0.36	ambiguous	0.417	ambiguous	-1.019	Destabilizing	1.0	D	0.687	prob.neutral	N	0.486657172	None	None	N
K/R	0.1148	likely_benign	0.1195	benign	-0.767	Destabilizing	0.999	D	0.61	neutral	N	0.51016875	None	None	N
K/S	0.7071	likely_pathogenic	0.7835	pathogenic	-1.458	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
K/T	0.4059	ambiguous	0.4976	ambiguous	-1.155	Destabilizing	1.0	D	0.782	deleterious	N	0.447117349	None	None	N
K/V	0.6735	likely_pathogenic	0.7504	pathogenic	-0.026	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/W	0.8717	likely_pathogenic	0.9152	pathogenic	-0.419	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
K/Y	0.6923	likely_pathogenic	0.7713	pathogenic	-0.054	Destabilizing	1.0	D	0.841	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.