TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17109	51550;51551;51552	chr2:178610201;178610200;178610199	chr2:179474928;179474927;179474926
N2AB	15468	46627;46628;46629	chr2:178610201;178610200;178610199	chr2:179474928;179474927;179474926
N2A	14541	43846;43847;43848	chr2:178610201;178610200;178610199	chr2:179474928;179474927;179474926
N2B	8044	24355;24356;24357	chr2:178610201;178610200;178610199	chr2:179474928;179474927;179474926
Novex-1	8169	24730;24731;24732	chr2:178610201;178610200;178610199	chr2:179474928;179474927;179474926
Novex-2	8236	24931;24932;24933	chr2:178610201;178610200;178610199	chr2:179474928;179474927;179474926
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: Fn3-12
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.4274
• 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/E	None	None	0.999	N	0.594	0.421	0.307016933798	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6156	likely_pathogenic	0.652	pathogenic	-0.137	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
K/C	0.8647	likely_pathogenic	0.8825	pathogenic	-0.229	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/D	0.762	likely_pathogenic	0.7922	pathogenic	0.252	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/E	0.3891	ambiguous	0.4452	ambiguous	0.28	Stabilizing	0.999	D	0.594	neutral	N	0.444213117	None	None	N
K/F	0.9461	likely_pathogenic	0.957	pathogenic	-0.238	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/G	0.6347	likely_pathogenic	0.6928	pathogenic	-0.376	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/H	0.4894	ambiguous	0.5151	ambiguous	-0.672	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/I	0.764	likely_pathogenic	0.7812	pathogenic	0.425	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
K/L	0.6846	likely_pathogenic	0.709	pathogenic	0.425	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/M	0.5527	ambiguous	0.5626	ambiguous	0.262	Stabilizing	1.0	D	0.75	deleterious	N	0.479143919	None	None	N
K/N	0.624	likely_pathogenic	0.6625	pathogenic	0.196	Stabilizing	1.0	D	0.709	prob.delet.	N	0.489793478	None	None	N
K/P	0.6905	likely_pathogenic	0.7227	pathogenic	0.267	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/Q	0.235	likely_benign	0.2604	benign	0.033	Stabilizing	1.0	D	0.689	prob.neutral	N	0.481347353	None	None	N
K/R	0.0989	likely_benign	0.1062	benign	-0.084	Destabilizing	0.999	D	0.527	neutral	N	0.488081324	None	None	N
K/S	0.6174	likely_pathogenic	0.6594	pathogenic	-0.388	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
K/T	0.3364	likely_benign	0.3376	benign	-0.191	Destabilizing	1.0	D	0.78	deleterious	N	0.416429082	None	None	N
K/V	0.6863	likely_pathogenic	0.6933	pathogenic	0.267	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
K/W	0.9046	likely_pathogenic	0.925	pathogenic	-0.194	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
K/Y	0.8756	likely_pathogenic	0.8982	pathogenic	0.145	Stabilizing	1.0	D	0.785	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.