TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31136	93631;93632;93633	chr2:178548220;178548219;178548218	chr2:179412947;179412946;179412945
N2AB	29495	88708;88709;88710	chr2:178548220;178548219;178548218	chr2:179412947;179412946;179412945
N2A	28568	85927;85928;85929	chr2:178548220;178548219;178548218	chr2:179412947;179412946;179412945
N2B	22071	66436;66437;66438	chr2:178548220;178548219;178548218	chr2:179412947;179412946;179412945
Novex-1	22196	66811;66812;66813	chr2:178548220;178548219;178548218	chr2:179412947;179412946;179412945
Novex-2	22263	67012;67013;67014	chr2:178548220;178548219;178548218	chr2:179412947;179412946;179412945
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: Fn3-115
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6507
• 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/I	rs1697982034	None	1.0	N	0.797	0.594	0.539970339866	gnomAD-4.0.0	1.27286E-05	None	None	None	None	N	None	0	0	None	0	2.21803E-04	None	0	0	0	0	0
K/N	None	None	1.0	N	0.718	0.383	0.18995819373	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.8825	likely_pathogenic	0.8438	pathogenic	-0.443	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
K/C	0.9398	likely_pathogenic	0.9317	pathogenic	-0.496	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/D	0.9826	likely_pathogenic	0.9746	pathogenic	-0.074	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/E	0.8665	likely_pathogenic	0.8066	pathogenic	0.034	Stabilizing	0.999	D	0.608	neutral	N	0.498162245	None	None	N
K/F	0.9705	likely_pathogenic	0.9635	pathogenic	-0.146	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
K/G	0.9468	likely_pathogenic	0.9325	pathogenic	-0.785	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/H	0.7215	likely_pathogenic	0.6827	pathogenic	-0.955	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/I	0.8689	likely_pathogenic	0.83	pathogenic	0.433	Stabilizing	1.0	D	0.797	deleterious	N	0.490131376	None	None	N
K/L	0.7708	likely_pathogenic	0.7114	pathogenic	0.433	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/M	0.745	likely_pathogenic	0.6861	pathogenic	0.111	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
K/N	0.959	likely_pathogenic	0.9436	pathogenic	-0.343	Destabilizing	1.0	D	0.718	prob.delet.	N	0.474015357	None	None	N
K/P	0.6111	likely_pathogenic	0.5734	pathogenic	0.171	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/Q	0.4824	ambiguous	0.4217	ambiguous	-0.356	Destabilizing	1.0	D	0.698	prob.neutral	N	0.508899313	None	None	N
K/R	0.1199	likely_benign	0.1179	benign	-0.431	Destabilizing	0.999	D	0.58	neutral	N	0.502992061	None	None	N
K/S	0.9418	likely_pathogenic	0.9226	pathogenic	-0.926	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/T	0.8448	likely_pathogenic	0.7965	pathogenic	-0.615	Destabilizing	1.0	D	0.776	deleterious	N	0.46930487	None	None	N
K/V	0.8418	likely_pathogenic	0.7956	pathogenic	0.171	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/W	0.9538	likely_pathogenic	0.9521	pathogenic	-0.08	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Y	0.9267	likely_pathogenic	0.9158	pathogenic	0.196	Stabilizing	1.0	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.