TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27133	81622;81623;81624	chr2:178564735;178564734;178564733	chr2:179429462;179429461;179429460
N2AB	25492	76699;76700;76701	chr2:178564735;178564734;178564733	chr2:179429462;179429461;179429460
N2A	24565	73918;73919;73920	chr2:178564735;178564734;178564733	chr2:179429462;179429461;179429460
N2B	18068	54427;54428;54429	chr2:178564735;178564734;178564733	chr2:179429462;179429461;179429460
Novex-1	18193	54802;54803;54804	chr2:178564735;178564734;178564733	chr2:179429462;179429461;179429460
Novex-2	18260	55003;55004;55005	chr2:178564735;178564734;178564733	chr2:179429462;179429461;179429460
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: Fn3-85
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4305
• 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	0.014	N	0.338	0.189	0.24896430686	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	2.29043E-05	None	0	0	None	0	0	0	0	0
K/R	None	None	0.014	N	0.213	0.065	0.183819452728	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	0.6476	likely_pathogenic	0.6536	pathogenic	-0.472	Destabilizing	0.86	D	0.572	neutral	None	None	None	None	N
K/C	0.7544	likely_pathogenic	0.7493	pathogenic	-0.535	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
K/D	0.9204	likely_pathogenic	0.9228	pathogenic	0.156	Stabilizing	0.754	D	0.635	neutral	None	None	None	None	N
K/E	0.4886	ambiguous	0.5118	ambiguous	0.249	Stabilizing	0.014	N	0.338	neutral	N	0.464999229	None	None	N
K/F	0.8804	likely_pathogenic	0.8732	pathogenic	-0.275	Destabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
K/G	0.8271	likely_pathogenic	0.828	pathogenic	-0.799	Destabilizing	0.86	D	0.643	neutral	None	None	None	None	N
K/H	0.4188	ambiguous	0.4059	ambiguous	-1.062	Destabilizing	0.994	D	0.69	prob.neutral	None	None	None	None	N
K/I	0.4689	ambiguous	0.4758	ambiguous	0.353	Stabilizing	0.97	D	0.744	deleterious	N	0.48057227	None	None	N
K/L	0.4885	ambiguous	0.4852	ambiguous	0.353	Stabilizing	0.956	D	0.646	neutral	None	None	None	None	N
K/M	0.3865	ambiguous	0.3994	ambiguous	0.144	Stabilizing	0.998	D	0.675	neutral	None	None	None	None	N
K/N	0.8048	likely_pathogenic	0.8131	pathogenic	-0.276	Destabilizing	0.942	D	0.556	neutral	N	0.472178479	None	None	N
K/P	0.8498	likely_pathogenic	0.8525	pathogenic	0.109	Stabilizing	0.978	D	0.704	prob.neutral	None	None	None	None	N
K/Q	0.2143	likely_benign	0.2227	benign	-0.345	Destabilizing	0.89	D	0.555	neutral	N	0.472178479	None	None	N
K/R	0.0826	likely_benign	0.0781	benign	-0.413	Destabilizing	0.014	N	0.213	neutral	N	0.483944941	None	None	N
K/S	0.7368	likely_pathogenic	0.7397	pathogenic	-0.936	Destabilizing	0.86	D	0.518	neutral	None	None	None	None	N
K/T	0.3666	ambiguous	0.3765	ambiguous	-0.642	Destabilizing	0.942	D	0.67	neutral	N	0.466719043	None	None	N
K/V	0.4588	ambiguous	0.4581	ambiguous	0.109	Stabilizing	0.978	D	0.7	prob.neutral	None	None	None	None	N
K/W	0.8467	likely_pathogenic	0.821	pathogenic	-0.162	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
K/Y	0.7633	likely_pathogenic	0.749	pathogenic	0.129	Stabilizing	0.993	D	0.753	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.