TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32524	97795;97796;97797	chr2:178541507;178541506;178541505	chr2:179406234;179406233;179406232
N2AB	30883	92872;92873;92874	chr2:178541507;178541506;178541505	chr2:179406234;179406233;179406232
N2A	29956	90091;90092;90093	chr2:178541507;178541506;178541505	chr2:179406234;179406233;179406232
N2B	23459	70600;70601;70602	chr2:178541507;178541506;178541505	chr2:179406234;179406233;179406232
Novex-1	23584	70975;70976;70977	chr2:178541507;178541506;178541505	chr2:179406234;179406233;179406232
Novex-2	23651	71176;71177;71178	chr2:178541507;178541506;178541505	chr2:179406234;179406233;179406232
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-125
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8985
• 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	0.939	N	0.547	0.299	0.392395365052	gnomAD-4.0.0	1.59264E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86041E-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
E/A	0.1	likely_benign	0.1098	benign	0.004	Stabilizing	0.939	D	0.532	neutral	N	0.436903142	None	None	N
E/C	0.6038	likely_pathogenic	0.6747	pathogenic	-0.163	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
E/D	0.1228	likely_benign	0.117	benign	-0.207	Destabilizing	0.046	N	0.26	neutral	N	0.423859274	None	None	N
E/F	0.5576	ambiguous	0.6114	pathogenic	-0.086	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
E/G	0.1029	likely_benign	0.1406	benign	-0.107	Destabilizing	0.046	N	0.346	neutral	N	0.510824898	None	None	N
E/H	0.3045	likely_benign	0.336	benign	0.502	Stabilizing	0.999	D	0.518	neutral	None	None	None	None	N
E/I	0.2149	likely_benign	0.2267	benign	0.238	Stabilizing	0.993	D	0.645	neutral	None	None	None	None	N
E/K	0.0801	likely_benign	0.0955	benign	0.379	Stabilizing	0.939	D	0.547	neutral	N	0.441866245	None	None	N
E/L	0.2301	likely_benign	0.2568	benign	0.238	Stabilizing	0.993	D	0.645	neutral	None	None	None	None	N
E/M	0.295	likely_benign	0.3259	benign	-0.003	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
E/N	0.1979	likely_benign	0.208	benign	0.269	Stabilizing	0.973	D	0.507	neutral	None	None	None	None	N
E/P	0.3593	ambiguous	0.41	ambiguous	0.178	Stabilizing	0.993	D	0.523	neutral	None	None	None	None	N
E/Q	0.1021	likely_benign	0.1155	benign	0.261	Stabilizing	0.991	D	0.5	neutral	N	0.489294832	None	None	N
E/R	0.1231	likely_benign	0.1564	benign	0.611	Stabilizing	0.993	D	0.533	neutral	None	None	None	None	N
E/S	0.1369	likely_benign	0.1549	benign	0.083	Stabilizing	0.953	D	0.53	neutral	None	None	None	None	N
E/T	0.1468	likely_benign	0.1577	benign	0.175	Stabilizing	0.993	D	0.455	neutral	None	None	None	None	N
E/V	0.1351	likely_benign	0.1409	benign	0.178	Stabilizing	0.991	D	0.589	neutral	N	0.472671941	None	None	N
E/W	0.6815	likely_pathogenic	0.761	pathogenic	-0.057	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.4436	ambiguous	0.4917	ambiguous	0.136	Stabilizing	0.998	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.