TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27358	82297;82298;82299	chr2:178564060;178564059;178564058	chr2:179428787;179428786;179428785
N2AB	25717	77374;77375;77376	chr2:178564060;178564059;178564058	chr2:179428787;179428786;179428785
N2A	24790	74593;74594;74595	chr2:178564060;178564059;178564058	chr2:179428787;179428786;179428785
N2B	18293	55102;55103;55104	chr2:178564060;178564059;178564058	chr2:179428787;179428786;179428785
Novex-1	18418	55477;55478;55479	chr2:178564060;178564059;178564058	chr2:179428787;179428786;179428785
Novex-2	18485	55678;55679;55680	chr2:178564060;178564059;178564058	chr2:179428787;179428786;179428785
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-140
• Domain position: 81
• Structural Position: 166
• Q(SASA): 0.5957
• 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/T	rs1483331348	0.024	0.988	N	0.676	0.391	0.42573502686	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/T	rs1483331348	0.024	0.988	N	0.676	0.391	0.42573502686	gnomAD-4.0.0	2.05265E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69848E-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	0.3376	likely_benign	0.3947	ambiguous	-0.029	Destabilizing	0.968	D	0.604	neutral	None	None	None	None	I
K/C	0.6774	likely_pathogenic	0.6948	pathogenic	-0.41	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
K/D	0.7878	likely_pathogenic	0.8381	pathogenic	0.194	Stabilizing	0.938	D	0.669	neutral	None	None	None	None	I
K/E	0.2769	likely_benign	0.3487	ambiguous	0.217	Stabilizing	0.067	N	0.307	neutral	N	0.492730287	None	None	I
K/F	0.8419	likely_pathogenic	0.8765	pathogenic	-0.219	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
K/G	0.6476	likely_pathogenic	0.7034	pathogenic	-0.233	Destabilizing	0.991	D	0.672	neutral	None	None	None	None	I
K/H	0.3994	ambiguous	0.4331	ambiguous	-0.431	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	I
K/I	0.3743	ambiguous	0.4492	ambiguous	0.428	Stabilizing	0.995	D	0.739	prob.delet.	None	None	None	None	I
K/L	0.4431	ambiguous	0.5317	ambiguous	0.428	Stabilizing	0.991	D	0.67	neutral	None	None	None	None	I
K/M	0.2845	likely_benign	0.342	ambiguous	0.105	Stabilizing	0.999	D	0.655	neutral	N	0.498178405	None	None	I
K/N	0.6314	likely_pathogenic	0.696	pathogenic	0.052	Stabilizing	0.988	D	0.65	neutral	D	0.525997499	None	None	I
K/P	0.9761	likely_pathogenic	0.9807	pathogenic	0.304	Stabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
K/Q	0.1594	likely_benign	0.1843	benign	-0.063	Destabilizing	0.976	D	0.66	neutral	N	0.484540694	None	None	I
K/R	0.0848	likely_benign	0.0872	benign	-0.067	Destabilizing	0.958	D	0.563	neutral	N	0.45552148	None	None	I
K/S	0.5228	ambiguous	0.5857	pathogenic	-0.459	Destabilizing	0.968	D	0.605	neutral	None	None	None	None	I
K/T	0.2039	likely_benign	0.2449	benign	-0.278	Destabilizing	0.988	D	0.676	prob.neutral	N	0.480571854	None	None	I
K/V	0.2936	likely_benign	0.3527	ambiguous	0.304	Stabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	I
K/W	0.887	likely_pathogenic	0.9029	pathogenic	-0.241	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
K/Y	0.7393	likely_pathogenic	0.7728	pathogenic	0.119	Stabilizing	0.998	D	0.719	prob.delet.	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.