TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21670	65233;65234;65235	chr2:178584543;178584542;178584541	chr2:179449270;179449269;179449268
N2AB	20029	60310;60311;60312	chr2:178584543;178584542;178584541	chr2:179449270;179449269;179449268
N2A	19102	57529;57530;57531	chr2:178584543;178584542;178584541	chr2:179449270;179449269;179449268
N2B	12605	38038;38039;38040	chr2:178584543;178584542;178584541	chr2:179449270;179449269;179449268
Novex-1	12730	38413;38414;38415	chr2:178584543;178584542;178584541	chr2:179449270;179449269;179449268
Novex-2	12797	38614;38615;38616	chr2:178584543;178584542;178584541	chr2:179449270;179449269;179449268
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: Fn3-45
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5184
• 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	rs1380994472	-0.078	0.958	N	0.483	0.234	0.347879110917	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs1380994472	-0.078	0.958	N	0.483	0.234	0.347879110917	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1380994472	-0.078	0.958	N	0.483	0.234	0.347879110917	gnomAD-4.0.0	3.84819E-06	None	None	None	None	N	None	5.07803E-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	0.4369	ambiguous	0.48	ambiguous	-0.417	Destabilizing	0.968	D	0.505	neutral	None	None	None	None	N
K/C	0.7848	likely_pathogenic	0.7966	pathogenic	-0.479	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
K/D	0.7152	likely_pathogenic	0.7583	pathogenic	0.079	Stabilizing	0.938	D	0.56	neutral	None	None	None	None	N
K/E	0.3512	ambiguous	0.3983	ambiguous	0.199	Stabilizing	0.067	N	0.243	neutral	N	0.412041983	None	None	N
K/F	0.9031	likely_pathogenic	0.9147	pathogenic	-0.11	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
K/G	0.5755	likely_pathogenic	0.6149	pathogenic	-0.764	Destabilizing	0.991	D	0.507	neutral	None	None	None	None	N
K/H	0.3733	ambiguous	0.3967	ambiguous	-0.915	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
K/I	0.6799	likely_pathogenic	0.7267	pathogenic	0.475	Stabilizing	0.994	D	0.655	neutral	N	0.477965377	None	None	N
K/L	0.6002	likely_pathogenic	0.6338	pathogenic	0.475	Stabilizing	0.991	D	0.507	neutral	None	None	None	None	N
K/M	0.425	ambiguous	0.4627	ambiguous	0.112	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	N
K/N	0.6232	likely_pathogenic	0.6684	pathogenic	-0.314	Destabilizing	0.988	D	0.57	neutral	N	0.455390115	None	None	N
K/P	0.9695	likely_pathogenic	0.9752	pathogenic	0.207	Stabilizing	0.995	D	0.641	neutral	None	None	None	None	N
K/Q	0.1996	likely_benign	0.2185	benign	-0.291	Destabilizing	0.976	D	0.566	neutral	N	0.502914703	None	None	N
K/R	0.0787	likely_benign	0.0815	benign	-0.359	Destabilizing	0.958	D	0.483	neutral	N	0.484155584	None	None	N
K/S	0.5337	ambiguous	0.5822	pathogenic	-0.912	Destabilizing	0.968	D	0.518	neutral	None	None	None	None	N
K/T	0.3164	likely_benign	0.3641	ambiguous	-0.583	Destabilizing	0.988	D	0.577	neutral	N	0.490889556	None	None	N
K/V	0.516	ambiguous	0.5663	pathogenic	0.207	Stabilizing	0.995	D	0.577	neutral	None	None	None	None	N
K/W	0.8659	likely_pathogenic	0.8695	pathogenic	-0.055	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
K/Y	0.7699	likely_pathogenic	0.7862	pathogenic	0.237	Stabilizing	0.998	D	0.597	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.