TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7032	21319;21320;21321	chr2:178724281;178724280;178724279	chr2:179589008;179589007;179589006
N2AB	6715	20368;20369;20370	chr2:178724281;178724280;178724279	chr2:179589008;179589007;179589006
N2A	5788	17587;17588;17589	chr2:178724281;178724280;178724279	chr2:179589008;179589007;179589006
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-54
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.5277
• 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
T/R	rs1361147832	-0.058	0.976	N	0.601	0.355	0.591083742983	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/R	rs1361147832	-0.058	0.976	N	0.601	0.355	0.591083742983	gnomAD-4.0.0	4.7913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29781E-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
T/A	0.1026	likely_benign	0.0984	benign	-0.477	Destabilizing	0.061	N	0.185	neutral	N	0.467719986	None	None	N
T/C	0.5533	ambiguous	0.5532	ambiguous	-0.126	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
T/D	0.3979	ambiguous	0.3743	ambiguous	-0.071	Destabilizing	0.884	D	0.55	neutral	None	None	None	None	N
T/E	0.2563	likely_benign	0.2473	benign	-0.149	Destabilizing	0.079	N	0.265	neutral	None	None	None	None	N
T/F	0.2747	likely_benign	0.2397	benign	-0.952	Destabilizing	0.982	D	0.666	neutral	None	None	None	None	N
T/G	0.3467	ambiguous	0.3279	benign	-0.617	Destabilizing	0.884	D	0.597	neutral	None	None	None	None	N
T/H	0.2577	likely_benign	0.2513	benign	-1.019	Destabilizing	0.997	D	0.641	neutral	None	None	None	None	N
T/I	0.2127	likely_benign	0.1975	benign	-0.219	Destabilizing	0.988	D	0.607	neutral	N	0.493541151	None	None	N
T/K	0.1724	likely_benign	0.1676	benign	-0.381	Destabilizing	0.92	D	0.548	neutral	N	0.470930863	None	None	N
T/L	0.137	likely_benign	0.1198	benign	-0.219	Destabilizing	0.939	D	0.532	neutral	None	None	None	None	N
T/M	0.0989	likely_benign	0.0951	benign	0.183	Stabilizing	0.997	D	0.591	neutral	None	None	None	None	N
T/N	0.1614	likely_benign	0.1515	benign	-0.094	Destabilizing	0.969	D	0.563	neutral	None	None	None	None	N
T/P	0.2507	likely_benign	0.2022	benign	-0.277	Destabilizing	0.988	D	0.607	neutral	N	0.493887867	None	None	N
T/Q	0.1999	likely_benign	0.198	benign	-0.407	Destabilizing	0.982	D	0.601	neutral	None	None	None	None	N
T/R	0.1415	likely_benign	0.1298	benign	-0.083	Destabilizing	0.976	D	0.601	neutral	N	0.463044885	None	None	N
T/S	0.1092	likely_benign	0.1093	benign	-0.301	Destabilizing	0.704	D	0.505	neutral	N	0.3866029	None	None	N
T/V	0.1608	likely_benign	0.1534	benign	-0.277	Destabilizing	0.939	D	0.497	neutral	None	None	None	None	N
T/W	0.6336	likely_pathogenic	0.5715	pathogenic	-0.915	Destabilizing	0.1	N	0.449	neutral	None	None	None	None	N
T/Y	0.3278	likely_benign	0.2999	benign	-0.647	Destabilizing	0.982	D	0.667	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.