TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19151	57676;57677;57678	chr2:178597631;178597630;178597629	chr2:179462358;179462357;179462356
N2AB	17510	52753;52754;52755	chr2:178597631;178597630;178597629	chr2:179462358;179462357;179462356
N2A	16583	49972;49973;49974	chr2:178597631;178597630;178597629	chr2:179462358;179462357;179462356
N2B	10086	30481;30482;30483	chr2:178597631;178597630;178597629	chr2:179462358;179462357;179462356
Novex-1	10211	30856;30857;30858	chr2:178597631;178597630;178597629	chr2:179462358;179462357;179462356
Novex-2	10278	31057;31058;31059	chr2:178597631;178597630;178597629	chr2:179462358;179462357;179462356
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-117
• Domain position: 57
• Structural Position: 141
• Q(SASA): 0.916
• 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/N	rs1362897659	0.278	0.982	N	0.506	0.31	0.238096912614	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/N	rs1362897659	0.278	0.982	N	0.506	0.31	0.238096912614	gnomAD-4.0.0	1.59253E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86007E-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	0.732	likely_pathogenic	0.7624	pathogenic	0.007	Stabilizing	0.953	D	0.563	neutral	None	None	None	None	N
K/C	0.8887	likely_pathogenic	0.8966	pathogenic	-0.233	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
K/D	0.8653	likely_pathogenic	0.8818	pathogenic	0.133	Stabilizing	0.993	D	0.544	neutral	None	None	None	None	N
K/E	0.4381	ambiguous	0.4899	ambiguous	0.159	Stabilizing	0.939	D	0.553	neutral	N	0.490191414	None	None	N
K/F	0.9656	likely_pathogenic	0.9664	pathogenic	-0.087	Destabilizing	0.986	D	0.649	neutral	None	None	None	None	N
K/G	0.732	likely_pathogenic	0.757	pathogenic	-0.227	Destabilizing	0.993	D	0.492	neutral	None	None	None	None	N
K/H	0.5422	ambiguous	0.5417	ambiguous	-0.488	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	N
K/I	0.849	likely_pathogenic	0.8561	pathogenic	0.552	Stabilizing	0.973	D	0.649	neutral	None	None	None	None	N
K/L	0.7375	likely_pathogenic	0.7659	pathogenic	0.552	Stabilizing	0.91	D	0.545	neutral	None	None	None	None	N
K/M	0.6626	likely_pathogenic	0.7024	pathogenic	0.282	Stabilizing	0.76	D	0.487	neutral	N	0.502888893	None	None	N
K/N	0.7648	likely_pathogenic	0.7813	pathogenic	0.166	Stabilizing	0.982	D	0.506	neutral	N	0.50883589	None	None	N
K/P	0.6871	likely_pathogenic	0.7317	pathogenic	0.4	Stabilizing	0.998	D	0.55	neutral	None	None	None	None	N
K/Q	0.2402	likely_benign	0.2532	benign	0.018	Stabilizing	0.982	D	0.507	neutral	N	0.512566842	None	None	N
K/R	0.0954	likely_benign	0.0954	benign	-0.084	Destabilizing	0.1	N	0.373	neutral	N	0.463332887	None	None	N
K/S	0.7377	likely_pathogenic	0.7602	pathogenic	-0.349	Destabilizing	0.953	D	0.527	neutral	None	None	None	None	N
K/T	0.4839	ambiguous	0.5249	ambiguous	-0.162	Destabilizing	0.982	D	0.481	neutral	N	0.498157537	None	None	N
K/V	0.79	likely_pathogenic	0.8096	pathogenic	0.4	Stabilizing	0.91	D	0.495	neutral	None	None	None	None	N
K/W	0.911	likely_pathogenic	0.9114	pathogenic	-0.08	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/Y	0.8991	likely_pathogenic	0.8992	pathogenic	0.264	Stabilizing	0.998	D	0.611	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.