TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33425	100498;100499;100500	chr2:178536474;178536473;178536472	chr2:179401201;179401200;179401199
N2AB	31784	95575;95576;95577	chr2:178536474;178536473;178536472	chr2:179401201;179401200;179401199
N2A	30857	92794;92795;92796	chr2:178536474;178536473;178536472	chr2:179401201;179401200;179401199
N2B	24360	73303;73304;73305	chr2:178536474;178536473;178536472	chr2:179401201;179401200;179401199
Novex-1	24485	73678;73679;73680	chr2:178536474;178536473;178536472	chr2:179401201;179401200;179401199
Novex-2	24552	73879;73880;73881	chr2:178536474;178536473;178536472	chr2:179401201;179401200;179401199
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: Fn3-131
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5558
• Predicted PPI site: I

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/I	None	None	0.863	N	0.379	0.239	0.52090908611	gnomAD-4.0.0	6.93947E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.08188E-07	0	0
R/S	None	None	0.029	N	0.146	0.24	0.15556083564	gnomAD-4.0.0	1.6409E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.94254E-06	0	0
R/T	None	None	0.01	N	0.148	0.199	0.307966526162	gnomAD-4.0.0	6.93946E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.08188E-07	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	0.4468	ambiguous	0.5262	ambiguous	-0.063	Destabilizing	0.176	N	0.289	neutral	None	None	None	None	I
R/C	0.2191	likely_benign	0.2356	benign	-0.088	Destabilizing	0.995	D	0.32	neutral	None	None	None	None	I
R/D	0.7941	likely_pathogenic	0.8617	pathogenic	0.05	Stabilizing	0.704	D	0.382	neutral	None	None	None	None	I
R/E	0.4504	ambiguous	0.5308	ambiguous	0.144	Stabilizing	0.495	N	0.307	neutral	None	None	None	None	I
R/F	0.6805	likely_pathogenic	0.7432	pathogenic	-0.067	Destabilizing	0.944	D	0.353	neutral	None	None	None	None	I
R/G	0.3199	likely_benign	0.3914	ambiguous	-0.322	Destabilizing	0.425	N	0.359	neutral	N	0.45098716	None	None	I
R/H	0.154	likely_benign	0.1738	benign	-0.778	Destabilizing	0.981	D	0.395	neutral	None	None	None	None	I
R/I	0.2692	likely_benign	0.3173	benign	0.603	Stabilizing	0.863	D	0.379	neutral	N	0.381511219	None	None	I
R/K	0.1264	likely_benign	0.1264	benign	-0.094	Destabilizing	0.01	N	0.104	neutral	N	0.402635853	None	None	I
R/L	0.3045	likely_benign	0.3501	ambiguous	0.603	Stabilizing	0.329	N	0.373	neutral	None	None	None	None	I
R/M	0.3444	ambiguous	0.3889	ambiguous	0.134	Stabilizing	0.981	D	0.374	neutral	None	None	None	None	I
R/N	0.6066	likely_pathogenic	0.7071	pathogenic	0.278	Stabilizing	0.704	D	0.279	neutral	None	None	None	None	I
R/P	0.8705	likely_pathogenic	0.9066	pathogenic	0.404	Stabilizing	0.828	D	0.369	neutral	None	None	None	None	I
R/Q	0.1209	likely_benign	0.1304	benign	0.163	Stabilizing	0.704	D	0.35	neutral	None	None	None	None	I
R/S	0.5075	ambiguous	0.6011	pathogenic	-0.188	Destabilizing	0.029	N	0.146	neutral	N	0.384338094	None	None	I
R/T	0.2091	likely_benign	0.2676	benign	0.064	Stabilizing	0.01	N	0.148	neutral	N	0.351108167	None	None	I
R/V	0.3954	ambiguous	0.4616	ambiguous	0.404	Stabilizing	0.543	D	0.417	neutral	None	None	None	None	I
R/W	0.2882	likely_benign	0.3301	benign	0.019	Stabilizing	0.995	D	0.357	neutral	None	None	None	None	I
R/Y	0.5442	ambiguous	0.6198	pathogenic	0.389	Stabilizing	0.981	D	0.355	neutral	None	None	None	None	I

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.