TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32504	97735;97736;97737	chr2:178541567;178541566;178541565	chr2:179406294;179406293;179406292
N2AB	30863	92812;92813;92814	chr2:178541567;178541566;178541565	chr2:179406294;179406293;179406292
N2A	29936	90031;90032;90033	chr2:178541567;178541566;178541565	chr2:179406294;179406293;179406292
N2B	23439	70540;70541;70542	chr2:178541567;178541566;178541565	chr2:179406294;179406293;179406292
Novex-1	23564	70915;70916;70917	chr2:178541567;178541566;178541565	chr2:179406294;179406293;179406292
Novex-2	23631	71116;71117;71118	chr2:178541567;178541566;178541565	chr2:179406294;179406293;179406292
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-125
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.4025
• 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
E/K	rs768612570	-0.359	0.117	N	0.393	0.141	0.264081493735	gnomAD-2.1.1	1.65E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.00827E-04	None	0	9.12E-06	0
E/K	rs768612570	-0.359	0.117	N	0.393	0.141	0.264081493735	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.13565E-04	0
E/K	rs768612570	-0.359	0.117	N	0.393	0.141	0.264081493735	gnomAD-4.0.0	1.28914E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40974E-06	1.21898E-04	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
E/A	0.1249	likely_benign	0.1343	benign	-0.644	Destabilizing	0.027	N	0.411	neutral	N	0.476634966	None	None	N
E/C	0.6316	likely_pathogenic	0.6792	pathogenic	-0.451	Destabilizing	0.935	D	0.585	neutral	None	None	None	None	N
E/D	0.0891	likely_benign	0.0876	benign	-0.823	Destabilizing	None	N	0.101	neutral	N	0.462609663	None	None	N
E/F	0.6713	likely_pathogenic	0.7079	pathogenic	0.013	Stabilizing	0.791	D	0.593	neutral	None	None	None	None	N
E/G	0.089	likely_benign	0.1052	benign	-0.983	Destabilizing	None	N	0.3	neutral	N	0.395229878	None	None	N
E/H	0.3191	likely_benign	0.351	ambiguous	-0.079	Destabilizing	0.555	D	0.518	neutral	None	None	None	None	N
E/I	0.3475	ambiguous	0.3776	ambiguous	0.272	Stabilizing	0.555	D	0.612	neutral	None	None	None	None	N
E/K	0.1174	likely_benign	0.1439	benign	-0.399	Destabilizing	0.117	N	0.393	neutral	N	0.489044116	None	None	N
E/L	0.3288	likely_benign	0.3557	ambiguous	0.272	Stabilizing	0.149	N	0.611	neutral	None	None	None	None	N
E/M	0.3886	ambiguous	0.4292	ambiguous	0.459	Stabilizing	0.935	D	0.583	neutral	None	None	None	None	N
E/N	0.1582	likely_benign	0.1732	benign	-0.899	Destabilizing	0.081	N	0.415	neutral	None	None	None	None	N
E/P	0.4946	ambiguous	0.5622	ambiguous	-0.012	Destabilizing	0.555	D	0.605	neutral	None	None	None	None	N
E/Q	0.1178	likely_benign	0.1308	benign	-0.758	Destabilizing	0.117	N	0.499	neutral	N	0.458894567	None	None	N
E/R	0.1766	likely_benign	0.2117	benign	-0.035	Destabilizing	0.38	N	0.527	neutral	None	None	None	None	N
E/S	0.1254	likely_benign	0.1387	benign	-1.154	Destabilizing	0.003	N	0.114	neutral	None	None	None	None	N
E/T	0.1714	likely_benign	0.1887	benign	-0.871	Destabilizing	0.081	N	0.502	neutral	None	None	None	None	N
E/V	0.2089	likely_benign	0.2225	benign	-0.012	Destabilizing	0.211	N	0.628	neutral	N	0.481368782	None	None	N
E/W	0.7921	likely_pathogenic	0.8336	pathogenic	0.285	Stabilizing	0.935	D	0.635	neutral	None	None	None	None	N
E/Y	0.4528	ambiguous	0.4942	ambiguous	0.265	Stabilizing	0.791	D	0.593	neutral	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.