TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25193	75802;75803;75804	chr2:178570555;178570554;178570553	chr2:179435282;179435281;179435280
N2AB	23552	70879;70880;70881	chr2:178570555;178570554;178570553	chr2:179435282;179435281;179435280
N2A	22625	68098;68099;68100	chr2:178570555;178570554;178570553	chr2:179435282;179435281;179435280
N2B	16128	48607;48608;48609	chr2:178570555;178570554;178570553	chr2:179435282;179435281;179435280
Novex-1	16253	48982;48983;48984	chr2:178570555;178570554;178570553	chr2:179435282;179435281;179435280
Novex-2	16320	49183;49184;49185	chr2:178570555;178570554;178570553	chr2:179435282;179435281;179435280
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-134
• Domain position: 83
• Structural Position: 166
• Q(SASA): 0.3834
• 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
R/G	rs1175414210	-1.831	None	D	0.163	0.203	0.337135696972	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	2.28822E-05	None	0	0	None	0	0	0	0	0
R/S	None	None	0.012	N	0.353	0.088	0.223146558224	gnomAD-4.0.0	1.59229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85936E-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
R/A	0.2063	likely_benign	0.2347	benign	-0.061	Destabilizing	0.007	N	0.23	neutral	None	None	None	None	N
R/C	0.1284	likely_benign	0.1433	benign	-0.313	Destabilizing	0.676	D	0.467	neutral	None	None	None	None	N
R/D	0.54	ambiguous	0.5794	pathogenic	-0.079	Destabilizing	0.072	N	0.429	neutral	None	None	None	None	N
R/E	0.2646	likely_benign	0.2922	benign	-0.01	Destabilizing	0.016	N	0.238	neutral	None	None	None	None	N
R/F	0.3825	ambiguous	0.4386	ambiguous	-0.281	Destabilizing	0.214	N	0.52	neutral	None	None	None	None	N
R/G	0.1976	likely_benign	0.2126	benign	-0.255	Destabilizing	None	N	0.163	neutral	D	0.526266858	None	None	N
R/H	0.1079	likely_benign	0.1141	benign	-0.7	Destabilizing	0.356	N	0.38	neutral	None	None	None	None	N
R/I	0.1298	likely_benign	0.1611	benign	0.415	Stabilizing	0.01	N	0.516	neutral	N	0.463236886	None	None	N
R/K	0.0696	likely_benign	0.0688	benign	-0.155	Destabilizing	None	N	0.049	neutral	N	0.404207226	None	None	N
R/L	0.1647	likely_benign	0.188	benign	0.415	Stabilizing	0.016	N	0.357	neutral	None	None	None	None	N
R/M	0.1358	likely_benign	0.1534	benign	-0.059	Destabilizing	0.214	N	0.456	neutral	None	None	None	None	N
R/N	0.3593	ambiguous	0.3991	ambiguous	-0.01	Destabilizing	0.072	N	0.215	neutral	None	None	None	None	N
R/P	0.8871	likely_pathogenic	0.9023	pathogenic	0.277	Stabilizing	0.136	N	0.521	neutral	None	None	None	None	N
R/Q	0.0901	likely_benign	0.0933	benign	-0.083	Destabilizing	0.038	N	0.279	neutral	None	None	None	None	N
R/S	0.291	likely_benign	0.3222	benign	-0.369	Destabilizing	0.012	N	0.353	neutral	N	0.490402058	None	None	N
R/T	0.1198	likely_benign	0.1297	benign	-0.163	Destabilizing	0.024	N	0.349	neutral	N	0.461466018	None	None	N
R/V	0.1726	likely_benign	0.2056	benign	0.277	Stabilizing	None	N	0.21	neutral	None	None	None	None	N
R/W	0.2055	likely_benign	0.2315	benign	-0.335	Destabilizing	0.864	D	0.472	neutral	None	None	None	None	N
R/Y	0.2791	likely_benign	0.3279	benign	0.075	Stabilizing	0.356	N	0.511	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.