TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24508	73747;73748;73749	chr2:178572610;178572609;178572608	chr2:179437337;179437336;179437335
N2AB	22867	68824;68825;68826	chr2:178572610;178572609;178572608	chr2:179437337;179437336;179437335
N2A	21940	66043;66044;66045	chr2:178572610;178572609;178572608	chr2:179437337;179437336;179437335
N2B	15443	46552;46553;46554	chr2:178572610;178572609;178572608	chr2:179437337;179437336;179437335
Novex-1	15568	46927;46928;46929	chr2:178572610;178572609;178572608	chr2:179437337;179437336;179437335
Novex-2	15635	47128;47129;47130	chr2:178572610;178572609;178572608	chr2:179437337;179437336;179437335
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-132
• Domain position: 78
• Structural Position: 166
• Q(SASA): 0.5943
• 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
K/R	rs1559416294	None	0.944	N	0.581	0.33	0.4897983601	gnomAD-4.0.0	1.59229E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85984E-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
K/A	0.7568	likely_pathogenic	0.7047	pathogenic	0.021	Stabilizing	0.916	D	0.613	neutral	None	None	None	None	I
K/C	0.8935	likely_pathogenic	0.8694	pathogenic	-0.28	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
K/D	0.9726	likely_pathogenic	0.9628	pathogenic	0.063	Stabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	I
K/E	0.7747	likely_pathogenic	0.7196	pathogenic	0.048	Stabilizing	0.944	D	0.607	neutral	D	0.528285656	None	None	I
K/F	0.9776	likely_pathogenic	0.97	pathogenic	-0.344	Destabilizing	0.975	D	0.673	neutral	None	None	None	None	I
K/G	0.9185	likely_pathogenic	0.8899	pathogenic	-0.121	Destabilizing	0.987	D	0.624	neutral	None	None	None	None	I
K/H	0.703	likely_pathogenic	0.6588	pathogenic	-0.389	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	I
K/I	0.8019	likely_pathogenic	0.7705	pathogenic	0.304	Stabilizing	0.95	D	0.672	neutral	None	None	None	None	I
K/L	0.8307	likely_pathogenic	0.8008	pathogenic	0.304	Stabilizing	0.653	D	0.575	neutral	None	None	None	None	I
K/M	0.7318	likely_pathogenic	0.6842	pathogenic	0.155	Stabilizing	0.63	D	0.547	neutral	N	0.511838889	None	None	I
K/N	0.9309	likely_pathogenic	0.9106	pathogenic	0.21	Stabilizing	0.983	D	0.679	prob.neutral	N	0.50217765	None	None	I
K/P	0.9954	likely_pathogenic	0.9943	pathogenic	0.235	Stabilizing	0.996	D	0.667	neutral	None	None	None	None	I
K/Q	0.394	ambiguous	0.3425	ambiguous	0.027	Stabilizing	0.983	D	0.683	prob.neutral	N	0.493428238	None	None	I
K/R	0.1318	likely_benign	0.1184	benign	0.005	Stabilizing	0.944	D	0.581	neutral	N	0.492213696	None	None	I
K/S	0.8638	likely_pathogenic	0.8299	pathogenic	-0.247	Destabilizing	0.916	D	0.635	neutral	None	None	None	None	I
K/T	0.6299	likely_pathogenic	0.5804	pathogenic	-0.131	Destabilizing	0.967	D	0.664	neutral	N	0.490403271	None	None	I
K/V	0.6911	likely_pathogenic	0.6532	pathogenic	0.235	Stabilizing	0.845	D	0.633	neutral	None	None	None	None	I
K/W	0.984	likely_pathogenic	0.9769	pathogenic	-0.393	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/Y	0.9502	likely_pathogenic	0.9383	pathogenic	-0.016	Destabilizing	0.987	D	0.651	neutral	None	None	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.