TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31253	93982;93983;93984	chr2:178547869;178547868;178547867	chr2:179412596;179412595;179412594
N2AB	29612	89059;89060;89061	chr2:178547869;178547868;178547867	chr2:179412596;179412595;179412594
N2A	28685	86278;86279;86280	chr2:178547869;178547868;178547867	chr2:179412596;179412595;179412594
N2B	22188	66787;66788;66789	chr2:178547869;178547868;178547867	chr2:179412596;179412595;179412594
Novex-1	22313	67162;67163;67164	chr2:178547869;178547868;178547867	chr2:179412596;179412595;179412594
Novex-2	22380	67363;67364;67365	chr2:178547869;178547868;178547867	chr2:179412596;179412595;179412594
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-151
• Domain position: 36
• Structural Position: 52
• Q(SASA): 0.6763
• 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
E/K	rs767771567	0.261	0.998	N	0.539	0.351	0.215869574891	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	rs767771567	0.261	0.998	N	0.539	0.351	0.215869574891	gnomAD-4.0.0	3.1823E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71579E-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
E/A	0.2573	likely_benign	0.2757	benign	-0.305	Destabilizing	0.998	D	0.614	neutral	N	0.483933793	None	None	N
E/C	0.9343	likely_pathogenic	0.9391	pathogenic	-0.346	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/D	0.1085	likely_benign	0.1042	benign	-0.314	Destabilizing	0.434	N	0.29	neutral	N	0.394850584	None	None	N
E/F	0.9149	likely_pathogenic	0.9238	pathogenic	0.002	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/G	0.1728	likely_benign	0.1935	benign	-0.502	Destabilizing	0.999	D	0.624	neutral	N	0.378411333	None	None	N
E/H	0.6896	likely_pathogenic	0.7013	pathogenic	0.513	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/I	0.7086	likely_pathogenic	0.7207	pathogenic	0.183	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/K	0.331	likely_benign	0.3411	ambiguous	0.263	Stabilizing	0.998	D	0.539	neutral	N	0.467174829	None	None	N
E/L	0.7016	likely_pathogenic	0.718	pathogenic	0.183	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/M	0.6732	likely_pathogenic	0.6827	pathogenic	0.036	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
E/N	0.27	likely_benign	0.2535	benign	-0.231	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
E/P	0.7785	likely_pathogenic	0.8158	pathogenic	0.04	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/Q	0.2696	likely_benign	0.2734	benign	-0.152	Destabilizing	0.999	D	0.659	neutral	N	0.508618807	None	None	N
E/R	0.5151	ambiguous	0.5386	ambiguous	0.629	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/S	0.2996	likely_benign	0.2971	benign	-0.378	Destabilizing	0.997	D	0.568	neutral	None	None	None	None	N
E/T	0.3646	ambiguous	0.3772	ambiguous	-0.2	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/V	0.4799	ambiguous	0.4992	ambiguous	0.04	Stabilizing	1.0	D	0.647	neutral	N	0.460251244	None	None	N
E/W	0.9573	likely_pathogenic	0.9636	pathogenic	0.189	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/Y	0.783	likely_pathogenic	0.7945	pathogenic	0.253	Stabilizing	1.0	D	0.615	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.