TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23034	69325;69326;69327	chr2:178577235;178577234;178577233	chr2:179441962;179441961;179441960
N2AB	21393	64402;64403;64404	chr2:178577235;178577234;178577233	chr2:179441962;179441961;179441960
N2A	20466	61621;61622;61623	chr2:178577235;178577234;178577233	chr2:179441962;179441961;179441960
N2B	13969	42130;42131;42132	chr2:178577235;178577234;178577233	chr2:179441962;179441961;179441960
Novex-1	14094	42505;42506;42507	chr2:178577235;178577234;178577233	chr2:179441962;179441961;179441960
Novex-2	14161	42706;42707;42708	chr2:178577235;178577234;178577233	chr2:179441962;179441961;179441960
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-128
• Domain position: 85
• Structural Position: 173
• Q(SASA): 0.7239
• 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/Q	rs1347501041	None	0.782	N	0.666	0.184	0.190952846119	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
K/Q	rs1347501041	None	0.782	N	0.666	0.184	0.190952846119	gnomAD-4.0.0	6.58337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47158E-05	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	0.2888	likely_benign	0.2406	benign	-0.244	Destabilizing	0.575	D	0.671	neutral	None	None	None	None	N
K/C	0.5886	likely_pathogenic	0.4894	ambiguous	-0.385	Destabilizing	0.991	D	0.742	deleterious	None	None	None	None	N
K/D	0.4923	ambiguous	0.4241	ambiguous	0.193	Stabilizing	0.826	D	0.675	prob.neutral	None	None	None	None	N
K/E	0.1969	likely_benign	0.161	benign	0.218	Stabilizing	0.338	N	0.635	neutral	N	0.48666832	None	None	N
K/F	0.6256	likely_pathogenic	0.544	ambiguous	-0.386	Destabilizing	0.906	D	0.735	prob.delet.	None	None	None	None	N
K/G	0.4515	ambiguous	0.4079	ambiguous	-0.485	Destabilizing	0.575	D	0.681	prob.neutral	None	None	None	None	N
K/H	0.1888	likely_benign	0.1675	benign	-0.86	Destabilizing	0.004	N	0.354	neutral	None	None	None	None	N
K/I	0.2656	likely_benign	0.2136	benign	0.322	Stabilizing	0.906	D	0.733	prob.delet.	None	None	None	None	N
K/L	0.2765	likely_benign	0.2268	benign	0.322	Stabilizing	0.575	D	0.675	neutral	None	None	None	None	N
K/M	0.1659	likely_benign	0.1399	benign	0.279	Stabilizing	0.988	D	0.686	prob.neutral	D	0.531424748	None	None	N
K/N	0.2743	likely_benign	0.2311	benign	0.085	Stabilizing	0.505	D	0.639	neutral	N	0.465391757	None	None	N
K/P	0.6233	likely_pathogenic	0.5505	ambiguous	0.163	Stabilizing	0.906	D	0.719	prob.delet.	None	None	None	None	N
K/Q	0.1363	likely_benign	0.1162	benign	-0.147	Destabilizing	0.782	D	0.666	neutral	N	0.491076849	None	None	N
K/R	0.0875	likely_benign	0.0818	benign	-0.151	Destabilizing	0.003	N	0.265	neutral	N	0.467450628	None	None	N
K/S	0.3156	likely_benign	0.2741	benign	-0.549	Destabilizing	0.575	D	0.622	neutral	None	None	None	None	N
K/T	0.1234	likely_benign	0.1022	benign	-0.357	Destabilizing	0.782	D	0.677	prob.neutral	N	0.47781955	None	None	N
K/V	0.2689	likely_benign	0.2118	benign	0.163	Stabilizing	0.826	D	0.694	prob.neutral	None	None	None	None	N
K/W	0.6398	likely_pathogenic	0.561	ambiguous	-0.28	Destabilizing	0.991	D	0.724	prob.delet.	None	None	None	None	N
K/Y	0.5015	ambiguous	0.4379	ambiguous	0.065	Stabilizing	0.704	D	0.749	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.