TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18951	57076;57077;57078	chr2:178598859;178598858;178598857	chr2:179463586;179463585;179463584
N2AB	17310	52153;52154;52155	chr2:178598859;178598858;178598857	chr2:179463586;179463585;179463584
N2A	16383	49372;49373;49374	chr2:178598859;178598858;178598857	chr2:179463586;179463585;179463584
N2B	9886	29881;29882;29883	chr2:178598859;178598858;178598857	chr2:179463586;179463585;179463584
Novex-1	10011	30256;30257;30258	chr2:178598859;178598858;178598857	chr2:179463586;179463585;179463584
Novex-2	10078	30457;30458;30459	chr2:178598859;178598858;178598857	chr2:179463586;179463585;179463584
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-25
• Domain position: 68
• Structural Position: 94
• Q(SASA): 0.5553
• 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
T/I	None	None	0.997	N	0.799	0.453	0.432604763906	gnomAD-4.0.0	1.36877E-06	None	None	None	None	N	None	2.99061E-05	0	None	0	0	None	0	0	8.99643E-07	0	0
T/N	rs2052524114	None	0.993	N	0.645	0.311	0.369309618794	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs2052524114	None	0.993	N	0.645	0.311	0.369309618794	gnomAD-4.0.0	1.85971E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.5434E-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
T/A	0.111	likely_benign	0.1102	benign	-0.614	Destabilizing	0.898	D	0.471	neutral	N	0.516636149	None	None	N
T/C	0.4926	ambiguous	0.4966	ambiguous	-0.382	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/D	0.4018	ambiguous	0.4072	ambiguous	0.109	Stabilizing	0.995	D	0.749	deleterious	None	None	None	None	N
T/E	0.385	ambiguous	0.3803	ambiguous	0.059	Stabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	N
T/F	0.3784	ambiguous	0.359	ambiguous	-0.946	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
T/G	0.2374	likely_benign	0.2249	benign	-0.794	Destabilizing	0.966	D	0.655	neutral	None	None	None	None	N
T/H	0.3652	ambiguous	0.3302	benign	-1.027	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/I	0.2987	likely_benign	0.3026	benign	-0.247	Destabilizing	0.997	D	0.799	deleterious	N	0.480375368	None	None	N
T/K	0.3808	ambiguous	0.3535	ambiguous	-0.551	Destabilizing	0.995	D	0.75	deleterious	None	None	None	None	N
T/L	0.1494	likely_benign	0.1438	benign	-0.247	Destabilizing	0.983	D	0.665	neutral	None	None	None	None	N
T/M	0.1137	likely_benign	0.1226	benign	-0.022	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/N	0.125	likely_benign	0.1359	benign	-0.373	Destabilizing	0.993	D	0.645	neutral	N	0.472168933	None	None	N
T/P	0.1485	likely_benign	0.122	benign	-0.339	Destabilizing	0.997	D	0.797	deleterious	N	0.521945968	None	None	N
T/Q	0.2972	likely_benign	0.2748	benign	-0.579	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
T/R	0.3907	ambiguous	0.3381	benign	-0.251	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
T/S	0.1007	likely_benign	0.1056	benign	-0.639	Destabilizing	0.362	N	0.34	neutral	N	0.46732205	None	None	N
T/V	0.2117	likely_benign	0.2115	benign	-0.339	Destabilizing	0.983	D	0.551	neutral	None	None	None	None	N
T/W	0.7222	likely_pathogenic	0.6995	pathogenic	-0.899	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/Y	0.4352	ambiguous	0.4128	ambiguous	-0.65	Destabilizing	0.999	D	0.794	deleterious	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.