TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16271	49036;49037;49038	chr2:178614703;178614702;178614701	chr2:179479430;179479429;179479428
N2AB	14630	44113;44114;44115	chr2:178614703;178614702;178614701	chr2:179479430;179479429;179479428
N2A	13703	41332;41333;41334	chr2:178614703;178614702;178614701	chr2:179479430;179479429;179479428
N2B	7206	21841;21842;21843	chr2:178614703;178614702;178614701	chr2:179479430;179479429;179479428
Novex-1	7331	22216;22217;22218	chr2:178614703;178614702;178614701	chr2:179479430;179479429;179479428
Novex-2	7398	22417;22418;22419	chr2:178614703;178614702;178614701	chr2:179479430;179479429;179479428
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: Ig-110
• Domain position: 10
• Structural Position: 18
• Q(SASA): 0.805
• 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/E	rs2056978022	None	0.996	N	0.613	0.426	0.411265580357	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs2056978022	None	0.996	N	0.613	0.426	0.411265580357	gnomAD-4.0.0	6.58129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47241E-05	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	0.9088	likely_pathogenic	0.897	pathogenic	-0.017	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
K/C	0.9529	likely_pathogenic	0.9471	pathogenic	-0.337	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/D	0.9842	likely_pathogenic	0.9818	pathogenic	0.121	Stabilizing	0.998	D	0.622	neutral	None	None	None	None	N
K/E	0.8392	likely_pathogenic	0.798	pathogenic	0.137	Stabilizing	0.996	D	0.613	neutral	N	0.509962453	None	None	N
K/F	0.9812	likely_pathogenic	0.976	pathogenic	-0.199	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/G	0.9664	likely_pathogenic	0.9648	pathogenic	-0.22	Destabilizing	0.997	D	0.633	neutral	None	None	None	None	N
K/H	0.7358	likely_pathogenic	0.7066	pathogenic	-0.42	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
K/I	0.8736	likely_pathogenic	0.843	pathogenic	0.441	Stabilizing	1.0	D	0.713	prob.delet.	N	0.514094484	None	None	N
K/L	0.7837	likely_pathogenic	0.7592	pathogenic	0.441	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/M	0.7075	likely_pathogenic	0.6684	pathogenic	0.156	Stabilizing	1.0	D	0.648	neutral	None	None	None	None	N
K/N	0.9534	likely_pathogenic	0.9467	pathogenic	0.09	Stabilizing	0.884	D	0.392	neutral	N	0.512858401	None	None	N
K/P	0.9224	likely_pathogenic	0.9249	pathogenic	0.317	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/Q	0.4887	ambiguous	0.4442	ambiguous	-0.048	Destabilizing	0.999	D	0.661	neutral	N	0.510483256	None	None	N
K/R	0.1085	likely_benign	0.1084	benign	-0.071	Destabilizing	0.998	D	0.595	neutral	N	0.452411247	None	None	N
K/S	0.9607	likely_pathogenic	0.9555	pathogenic	-0.411	Destabilizing	0.997	D	0.635	neutral	None	None	None	None	N
K/T	0.802	likely_pathogenic	0.7628	pathogenic	-0.241	Destabilizing	0.999	D	0.615	neutral	N	0.51154725	None	None	N
K/V	0.8265	likely_pathogenic	0.792	pathogenic	0.317	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/W	0.9768	likely_pathogenic	0.9726	pathogenic	-0.219	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/Y	0.9513	likely_pathogenic	0.9438	pathogenic	0.135	Stabilizing	1.0	D	0.693	prob.neutral	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.