TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17312	52159;52160;52161	chr2:178609376;178609375;178609374	chr2:179474103;179474102;179474101
N2AB	15671	47236;47237;47238	chr2:178609376;178609375;178609374	chr2:179474103;179474102;179474101
N2A	14744	44455;44456;44457	chr2:178609376;178609375;178609374	chr2:179474103;179474102;179474101
N2B	8247	24964;24965;24966	chr2:178609376;178609375;178609374	chr2:179474103;179474102;179474101
Novex-1	8372	25339;25340;25341	chr2:178609376;178609375;178609374	chr2:179474103;179474102;179474101
Novex-2	8439	25540;25541;25542	chr2:178609376;178609375;178609374	chr2:179474103;179474102;179474101
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: Ig-112
• Domain position: 62
• Structural Position: 94
• Q(SASA): 0.3903
• 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/A	None	None	0.027	N	0.259	0.134	0.263140351381	gnomAD-4.0.0	1.20037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0
E/K	rs749451611	0.746	None	N	0.141	0.132	0.208816687407	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs749451611	0.746	None	N	0.141	0.132	0.208816687407	gnomAD-4.0.0	3.42426E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.64231E-05	1.65953E-05
E/Q	rs749451611	-0.416	None	N	0.168	0.049	0.239901079897	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs749451611	-0.416	None	N	0.168	0.049	0.239901079897	gnomAD-4.0.0	1.3697E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00014E-07	1.16058E-05	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	0.1009	likely_benign	0.1027	benign	0.024	Stabilizing	0.027	N	0.259	neutral	N	0.4811072	None	None	N
E/C	0.6769	likely_pathogenic	0.7072	pathogenic	-0.254	Destabilizing	0.935	D	0.318	neutral	None	None	None	None	N
E/D	0.1052	likely_benign	0.1158	benign	-0.369	Destabilizing	0.052	N	0.237	neutral	N	0.51756723	None	None	N
E/F	0.4582	ambiguous	0.4601	ambiguous	-0.075	Destabilizing	0.555	D	0.324	neutral	None	None	None	None	N
E/G	0.1145	likely_benign	0.1179	benign	-0.074	Destabilizing	None	N	0.181	neutral	N	0.482121158	None	None	N
E/H	0.3112	likely_benign	0.3301	benign	0.58	Stabilizing	0.38	N	0.265	neutral	None	None	None	None	N
E/I	0.1599	likely_benign	0.162	benign	0.22	Stabilizing	0.555	D	0.354	neutral	None	None	None	None	N
E/K	0.101	likely_benign	0.1019	benign	0.347	Stabilizing	None	N	0.141	neutral	N	0.514793496	None	None	N
E/L	0.1841	likely_benign	0.1825	benign	0.22	Stabilizing	0.149	N	0.337	neutral	None	None	None	None	N
E/M	0.2453	likely_benign	0.245	benign	-0.065	Destabilizing	0.824	D	0.314	neutral	None	None	None	None	N
E/N	0.1615	likely_benign	0.1679	benign	0.163	Stabilizing	0.081	N	0.185	neutral	None	None	None	None	N
E/P	0.2124	likely_benign	0.2252	benign	0.172	Stabilizing	0.555	D	0.279	neutral	None	None	None	None	N
E/Q	0.1084	likely_benign	0.12	benign	0.157	Stabilizing	None	N	0.168	neutral	N	0.48872719	None	None	N
E/R	0.1895	likely_benign	0.1888	benign	0.587	Stabilizing	0.081	N	0.199	neutral	None	None	None	None	N
E/S	0.1467	likely_benign	0.1509	benign	0.021	Stabilizing	0.002	N	0.118	neutral	None	None	None	None	N
E/T	0.1266	likely_benign	0.1289	benign	0.106	Stabilizing	0.081	N	0.254	neutral	None	None	None	None	N
E/V	0.1092	likely_benign	0.1113	benign	0.172	Stabilizing	0.117	N	0.314	neutral	N	0.482374647	None	None	N
E/W	0.74	likely_pathogenic	0.7679	pathogenic	-0.059	Destabilizing	0.935	D	0.349	neutral	None	None	None	None	N
E/Y	0.3716	ambiguous	0.4013	ambiguous	0.14	Stabilizing	0.555	D	0.343	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.