TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22135	66628;66629;66630	chr2:178581966;178581965;178581964	chr2:179446693;179446692;179446691
N2AB	20494	61705;61706;61707	chr2:178581966;178581965;178581964	chr2:179446693;179446692;179446691
N2A	19567	58924;58925;58926	chr2:178581966;178581965;178581964	chr2:179446693;179446692;179446691
N2B	13070	39433;39434;39435	chr2:178581966;178581965;178581964	chr2:179446693;179446692;179446691
Novex-1	13195	39808;39809;39810	chr2:178581966;178581965;178581964	chr2:179446693;179446692;179446691
Novex-2	13262	40009;40010;40011	chr2:178581966;178581965;178581964	chr2:179446693;179446692;179446691
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: Fn3-48
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5304
• 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/E	None	None	0.067	N	0.369	0.167	0.202949470691	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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	0.3374	likely_benign	0.3176	benign	0.009	Stabilizing	0.968	D	0.564	neutral	None	None	None	None	I
K/C	0.7856	likely_pathogenic	0.7814	pathogenic	-0.138	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
K/D	0.7321	likely_pathogenic	0.6977	pathogenic	0.001	Stabilizing	0.938	D	0.571	neutral	None	None	None	None	I
K/E	0.3054	likely_benign	0.2674	benign	-0.01	Destabilizing	0.067	N	0.369	neutral	N	0.422645766	None	None	I
K/F	0.862	likely_pathogenic	0.8453	pathogenic	-0.306	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
K/G	0.617	likely_pathogenic	0.6132	pathogenic	-0.162	Destabilizing	0.991	D	0.521	neutral	None	None	None	None	I
K/H	0.4301	ambiguous	0.4109	ambiguous	-0.497	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	I
K/I	0.3938	ambiguous	0.3637	ambiguous	0.376	Stabilizing	0.994	D	0.651	neutral	N	0.49235378	None	None	I
K/L	0.4048	ambiguous	0.3973	ambiguous	0.376	Stabilizing	0.991	D	0.533	neutral	None	None	None	None	I
K/M	0.3122	likely_benign	0.2813	benign	0.281	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	I
K/N	0.6001	likely_pathogenic	0.5731	pathogenic	0.291	Stabilizing	0.988	D	0.603	neutral	D	0.524002052	None	None	I
K/P	0.8036	likely_pathogenic	0.8312	pathogenic	0.281	Stabilizing	0.995	D	0.62	neutral	None	None	None	None	I
K/Q	0.1775	likely_benign	0.1642	benign	0.077	Stabilizing	0.976	D	0.587	neutral	N	0.491948348	None	None	I
K/R	0.0836	likely_benign	0.0858	benign	0.013	Stabilizing	0.958	D	0.46	neutral	N	0.4888894	None	None	I
K/S	0.547	ambiguous	0.5194	ambiguous	-0.175	Destabilizing	0.968	D	0.537	neutral	None	None	None	None	I
K/T	0.2719	likely_benign	0.2525	benign	-0.049	Destabilizing	0.988	D	0.573	neutral	N	0.479307125	None	None	I
K/V	0.3463	ambiguous	0.3199	benign	0.281	Stabilizing	0.995	D	0.601	neutral	None	None	None	None	I
K/W	0.8906	likely_pathogenic	0.8782	pathogenic	-0.33	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
K/Y	0.7649	likely_pathogenic	0.7385	pathogenic	0.039	Stabilizing	0.998	D	0.638	neutral	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.