TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14273	43042;43043;43044	chr2:178633542;178633541;178633540	chr2:179498269;179498268;179498267
N2AB	12632	38119;38120;38121	chr2:178633542;178633541;178633540	chr2:179498269;179498268;179498267
N2A	11705	35338;35339;35340	chr2:178633542;178633541;178633540	chr2:179498269;179498268;179498267
N2B	5208	15847;15848;15849	chr2:178633542;178633541;178633540	chr2:179498269;179498268;179498267
Novex-1	5333	16222;16223;16224	chr2:178633542;178633541;178633540	chr2:179498269;179498268;179498267
Novex-2	5400	16423;16424;16425	chr2:178633542;178633541;178633540	chr2:179498269;179498268;179498267
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-93
• Domain position: 43
• Structural Position: 111
• Q(SASA): 0.6757
• 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
P/S	rs1440872005	-0.251	None	N	0.137	0.098	0.0401082797425	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/S	rs1440872005	-0.251	None	N	0.137	0.098	0.0401082797425	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	2.28749E-05	None	0	0	None	0	0	0	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
P/A	0.0583	likely_benign	0.0577	benign	-0.369	Destabilizing	None	N	0.126	neutral	N	0.442537997	None	None	N
P/C	0.4843	ambiguous	0.41	ambiguous	-0.825	Destabilizing	0.245	N	0.314	neutral	None	None	None	None	N
P/D	0.1855	likely_benign	0.2072	benign	-0.234	Destabilizing	0.009	N	0.324	neutral	None	None	None	None	N
P/E	0.1434	likely_benign	0.1569	benign	-0.344	Destabilizing	0.009	N	0.363	neutral	None	None	None	None	N
P/F	0.4278	ambiguous	0.3303	benign	-0.658	Destabilizing	0.074	N	0.381	neutral	None	None	None	None	N
P/G	0.1517	likely_benign	0.1579	benign	-0.447	Destabilizing	0.004	N	0.368	neutral	None	None	None	None	N
P/H	0.1431	likely_benign	0.1404	benign	0.021	Stabilizing	0.196	N	0.309	neutral	N	0.455824607	None	None	N
P/I	0.2311	likely_benign	0.1716	benign	-0.308	Destabilizing	0.022	N	0.371	neutral	None	None	None	None	N
P/K	0.1346	likely_benign	0.1477	benign	-0.401	Destabilizing	None	N	0.122	neutral	None	None	None	None	N
P/L	0.1168	likely_benign	0.0908	benign	-0.308	Destabilizing	None	N	0.192	neutral	N	0.449437988	None	None	N
P/M	0.2298	likely_benign	0.1874	benign	-0.55	Destabilizing	0.074	N	0.309	neutral	None	None	None	None	N
P/N	0.1463	likely_benign	0.1374	benign	-0.234	Destabilizing	None	N	0.168	neutral	None	None	None	None	N
P/Q	0.0885	likely_benign	0.0935	benign	-0.431	Destabilizing	0.044	N	0.336	neutral	None	None	None	None	N
P/R	0.1411	likely_benign	0.1462	benign	0.062	Stabilizing	0.007	N	0.28	neutral	N	0.438564738	None	None	N
P/S	0.0777	likely_benign	0.0692	benign	-0.576	Destabilizing	None	N	0.137	neutral	N	0.410252742	None	None	N
P/T	0.0764	likely_benign	0.0621	benign	-0.589	Destabilizing	None	N	0.147	neutral	N	0.438632891	None	None	N
P/V	0.1539	likely_benign	0.1286	benign	-0.299	Destabilizing	0.009	N	0.324	neutral	None	None	None	None	N
P/W	0.5739	likely_pathogenic	0.5121	ambiguous	-0.714	Destabilizing	0.788	D	0.315	neutral	None	None	None	None	N
P/Y	0.369	ambiguous	0.3079	benign	-0.444	Destabilizing	0.245	N	0.38	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.