TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6295	19108;19109;19110	chr2:178729155;178729154;178729153	chr2:179593882;179593881;179593880
N2AB	5978	18157;18158;18159	chr2:178729155;178729154;178729153	chr2:179593882;179593881;179593880
N2A	5051	15376;15377;15378	chr2:178729155;178729154;178729153	chr2:179593882;179593881;179593880
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-47
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4674
• 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
I/V	None	None	None	N	0.056	0.117	0.0920862733494	gnomAD-4.0.0	3.34191E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.95948E-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
I/A	0.2186	likely_benign	0.1926	benign	-0.664	Destabilizing	0.007	N	0.141	neutral	None	None	None	None	I
I/C	0.5195	ambiguous	0.5274	ambiguous	-0.735	Destabilizing	0.356	N	0.274	neutral	None	None	None	None	I
I/D	0.5036	ambiguous	0.5029	ambiguous	0.133	Stabilizing	0.038	N	0.369	neutral	None	None	None	None	I
I/E	0.3106	likely_benign	0.3166	benign	0.065	Stabilizing	0.072	N	0.325	neutral	None	None	None	None	I
I/F	0.1425	likely_benign	0.1265	benign	-0.512	Destabilizing	0.055	N	0.234	neutral	N	0.452551789	None	None	I
I/G	0.4304	ambiguous	0.3898	ambiguous	-0.848	Destabilizing	0.016	N	0.271	neutral	None	None	None	None	I
I/H	0.2643	likely_benign	0.2631	benign	-0.033	Destabilizing	0.214	N	0.298	neutral	None	None	None	None	I
I/K	0.1669	likely_benign	0.1713	benign	-0.341	Destabilizing	0.038	N	0.321	neutral	None	None	None	None	I
I/L	0.0812	likely_benign	0.0785	benign	-0.294	Destabilizing	None	N	0.062	neutral	N	0.402181988	None	None	I
I/M	0.1003	likely_benign	0.0924	benign	-0.408	Destabilizing	0.171	N	0.242	neutral	N	0.485357945	None	None	I
I/N	0.1667	likely_benign	0.1678	benign	-0.235	Destabilizing	None	N	0.197	neutral	N	0.510312318	None	None	I
I/P	0.6359	likely_pathogenic	0.6214	pathogenic	-0.384	Destabilizing	0.136	N	0.393	neutral	None	None	None	None	I
I/Q	0.1855	likely_benign	0.1892	benign	-0.404	Destabilizing	0.214	N	0.403	neutral	None	None	None	None	I
I/R	0.1178	likely_benign	0.1268	benign	0.172	Stabilizing	0.072	N	0.393	neutral	None	None	None	None	I
I/S	0.1535	likely_benign	0.1533	benign	-0.769	Destabilizing	0.012	N	0.181	neutral	N	0.452957525	None	None	I
I/T	0.104	likely_benign	0.0982	benign	-0.723	Destabilizing	None	N	0.089	neutral	N	0.403222138	None	None	I
I/V	0.073	likely_benign	0.0689	benign	-0.384	Destabilizing	None	N	0.056	neutral	N	0.359449931	None	None	I
I/W	0.5919	likely_pathogenic	0.5937	pathogenic	-0.523	Destabilizing	0.864	D	0.293	neutral	None	None	None	None	I
I/Y	0.3362	likely_benign	0.3518	ambiguous	-0.283	Destabilizing	0.356	N	0.365	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.