TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17311	52156;52157;52158	chr2:178609379;178609378;178609377	chr2:179474106;179474105;179474104
N2AB	15670	47233;47234;47235	chr2:178609379;178609378;178609377	chr2:179474106;179474105;179474104
N2A	14743	44452;44453;44454	chr2:178609379;178609378;178609377	chr2:179474106;179474105;179474104
N2B	8246	24961;24962;24963	chr2:178609379;178609378;178609377	chr2:179474106;179474105;179474104
Novex-1	8371	25336;25337;25338	chr2:178609379;178609378;178609377	chr2:179474106;179474105;179474104
Novex-2	8438	25537;25538;25539	chr2:178609379;178609378;178609377	chr2:179474106;179474105;179474104
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: 61
• Structural Position: 93
• Q(SASA): 1.0157
• 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	None	None	0.051	N	0.274	0.192	0.304108284078	gnomAD-4.0.0	6.84824E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00003E-07	0	0
E/Q	None	None	0.801	N	0.427	0.141	0.407767136052	gnomAD-4.0.0	6.84824E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65926E-05

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	0.1196	likely_benign	0.1231	benign	0.005	Stabilizing	0.625	D	0.419	neutral	D	0.526573502	None	None	N
E/C	0.7449	likely_pathogenic	0.7803	pathogenic	-0.306	Destabilizing	0.998	D	0.446	neutral	None	None	None	None	N
E/D	0.0984	likely_benign	0.1056	benign	-0.358	Destabilizing	0.012	N	0.25	neutral	N	0.506947591	None	None	N
E/F	0.5774	likely_pathogenic	0.5908	pathogenic	-0.087	Destabilizing	0.991	D	0.435	neutral	None	None	None	None	N
E/G	0.1164	likely_benign	0.1252	benign	-0.09	Destabilizing	0.005	N	0.286	neutral	D	0.526053427	None	None	N
E/H	0.3884	ambiguous	0.4117	ambiguous	0.581	Stabilizing	0.991	D	0.403	neutral	None	None	None	None	N
E/I	0.2352	likely_benign	0.2415	benign	0.195	Stabilizing	0.974	D	0.454	neutral	None	None	None	None	N
E/K	0.1186	likely_benign	0.1234	benign	0.296	Stabilizing	0.051	N	0.274	neutral	N	0.487160814	None	None	N
E/L	0.2748	likely_benign	0.2785	benign	0.195	Stabilizing	0.974	D	0.461	neutral	None	None	None	None	N
E/M	0.3324	likely_benign	0.3442	ambiguous	-0.104	Destabilizing	0.998	D	0.442	neutral	None	None	None	None	N
E/N	0.1802	likely_benign	0.1965	benign	0.122	Stabilizing	0.728	D	0.396	neutral	None	None	None	None	N
E/P	0.2606	likely_benign	0.2729	benign	0.148	Stabilizing	0.974	D	0.459	neutral	None	None	None	None	N
E/Q	0.1431	likely_benign	0.1583	benign	0.118	Stabilizing	0.801	D	0.427	neutral	N	0.487667793	None	None	N
E/R	0.2163	likely_benign	0.2199	benign	0.546	Stabilizing	0.728	D	0.409	neutral	None	None	None	None	N
E/S	0.1631	likely_benign	0.1784	benign	-0.028	Destabilizing	0.688	D	0.401	neutral	None	None	None	None	N
E/T	0.1477	likely_benign	0.1548	benign	0.057	Stabilizing	0.842	D	0.484	neutral	None	None	None	None	N
E/V	0.1479	likely_benign	0.1466	benign	0.148	Stabilizing	0.966	D	0.472	neutral	N	0.488681751	None	None	N
E/W	0.7867	likely_pathogenic	0.81	pathogenic	-0.069	Destabilizing	0.998	D	0.487	neutral	None	None	None	None	N
E/Y	0.4714	ambiguous	0.4916	ambiguous	0.126	Stabilizing	0.991	D	0.454	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.