TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27708	83347;83348;83349	chr2:178563010;178563009;178563008	chr2:179427737;179427736;179427735
N2AB	26067	78424;78425;78426	chr2:178563010;178563009;178563008	chr2:179427737;179427736;179427735
N2A	25140	75643;75644;75645	chr2:178563010;178563009;178563008	chr2:179427737;179427736;179427735
N2B	18643	56152;56153;56154	chr2:178563010;178563009;178563008	chr2:179427737;179427736;179427735
Novex-1	18768	56527;56528;56529	chr2:178563010;178563009;178563008	chr2:179427737;179427736;179427735
Novex-2	18835	56728;56729;56730	chr2:178563010;178563009;178563008	chr2:179427737;179427736;179427735
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-141
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.3443
• 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/Q	None	None	0.942	N	0.551	0.338	0.342400092842	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/T	None	None	0.032	N	0.404	0.239	0.19670166235	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5297	ambiguous	0.4988	ambiguous	-0.328	Destabilizing	0.754	D	0.59	neutral	None	None	None	None	N
K/C	0.68	likely_pathogenic	0.664	pathogenic	-0.463	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
K/D	0.8448	likely_pathogenic	0.8196	pathogenic	0.011	Stabilizing	0.956	D	0.637	neutral	None	None	None	None	N
K/E	0.3701	ambiguous	0.3435	ambiguous	0.099	Stabilizing	0.822	D	0.533	neutral	N	0.508198385	None	None	N
K/F	0.8444	likely_pathogenic	0.8141	pathogenic	-0.087	Destabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	N
K/G	0.7585	likely_pathogenic	0.7258	pathogenic	-0.657	Destabilizing	0.86	D	0.639	neutral	None	None	None	None	N
K/H	0.2924	likely_benign	0.2726	benign	-0.896	Destabilizing	0.994	D	0.657	neutral	None	None	None	None	N
K/I	0.3648	ambiguous	0.3471	ambiguous	0.502	Stabilizing	0.942	D	0.714	prob.delet.	N	0.520573036	None	None	N
K/L	0.4412	ambiguous	0.4131	ambiguous	0.502	Stabilizing	0.754	D	0.64	neutral	None	None	None	None	N
K/M	0.2943	likely_benign	0.2747	benign	0.206	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	N
K/N	0.5748	likely_pathogenic	0.5331	ambiguous	-0.274	Destabilizing	0.942	D	0.542	neutral	N	0.4967596	None	None	N
K/P	0.9875	likely_pathogenic	0.9845	pathogenic	0.256	Stabilizing	0.978	D	0.663	neutral	None	None	None	None	N
K/Q	0.1664	likely_benign	0.1581	benign	-0.336	Destabilizing	0.942	D	0.551	neutral	N	0.484224753	None	None	N
K/R	0.092	likely_benign	0.0903	benign	-0.426	Destabilizing	0.014	N	0.263	neutral	N	0.484246877	None	None	N
K/S	0.5414	ambiguous	0.5113	ambiguous	-0.859	Destabilizing	0.754	D	0.507	neutral	None	None	None	None	N
K/T	0.1766	likely_benign	0.1637	benign	-0.577	Destabilizing	0.032	N	0.404	neutral	N	0.402495072	None	None	N
K/V	0.3645	ambiguous	0.3463	ambiguous	0.256	Stabilizing	0.915	D	0.642	neutral	None	None	None	None	N
K/W	0.855	likely_pathogenic	0.8234	pathogenic	-0.01	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
K/Y	0.7581	likely_pathogenic	0.7286	pathogenic	0.28	Stabilizing	0.993	D	0.717	prob.delet.	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.