TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22828	68707;68708;68709	chr2:178578033;178578032;178578031	chr2:179442760;179442759;179442758
N2AB	21187	63784;63785;63786	chr2:178578033;178578032;178578031	chr2:179442760;179442759;179442758
N2A	20260	61003;61004;61005	chr2:178578033;178578032;178578031	chr2:179442760;179442759;179442758
N2B	13763	41512;41513;41514	chr2:178578033;178578032;178578031	chr2:179442760;179442759;179442758
Novex-1	13888	41887;41888;41889	chr2:178578033;178578032;178578031	chr2:179442760;179442759;179442758
Novex-2	13955	42088;42089;42090	chr2:178578033;178578032;178578031	chr2:179442760;179442759;179442758
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: Fn3-53
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.8172
• 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/Q	None	None	0.999	N	0.741	0.255	0.280987212366	gnomAD-4.0.0	1.59267E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86062E-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	0.5261	ambiguous	0.49	ambiguous	-0.117	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	I
K/C	0.8053	likely_pathogenic	0.7852	pathogenic	-0.086	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
K/D	0.7451	likely_pathogenic	0.72	pathogenic	-0.069	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
K/E	0.3812	ambiguous	0.3345	benign	-0.031	Destabilizing	0.996	D	0.621	neutral	N	0.458950496	None	None	I
K/F	0.861	likely_pathogenic	0.8358	pathogenic	-0.071	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
K/G	0.6545	likely_pathogenic	0.6267	pathogenic	-0.391	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
K/H	0.4398	ambiguous	0.4177	ambiguous	-0.756	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
K/I	0.5597	ambiguous	0.5225	ambiguous	0.551	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
K/L	0.4792	ambiguous	0.4577	ambiguous	0.551	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	I
K/M	0.4094	ambiguous	0.3879	ambiguous	0.358	Stabilizing	1.0	D	0.708	prob.delet.	N	0.48035846	None	None	I
K/N	0.6137	likely_pathogenic	0.5827	pathogenic	0.116	Stabilizing	0.999	D	0.741	deleterious	N	0.477876471	None	None	I
K/P	0.5443	ambiguous	0.5135	ambiguous	0.358	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
K/Q	0.2189	likely_benign	0.1977	benign	-0.03	Destabilizing	0.999	D	0.741	deleterious	N	0.48477166	None	None	I
K/R	0.1004	likely_benign	0.0959	benign	-0.267	Destabilizing	0.884	D	0.325	neutral	N	0.51063011	None	None	I
K/S	0.6133	likely_pathogenic	0.5805	pathogenic	-0.363	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	I
K/T	0.4135	ambiguous	0.3917	ambiguous	-0.161	Destabilizing	0.999	D	0.713	prob.delet.	N	0.466266676	None	None	I
K/V	0.5111	ambiguous	0.4767	ambiguous	0.358	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
K/W	0.8673	likely_pathogenic	0.8491	pathogenic	-0.044	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
K/Y	0.7531	likely_pathogenic	0.7226	pathogenic	0.258	Stabilizing	1.0	D	0.755	deleterious	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.