TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6322	19189;19190;19191	chr2:178729074;178729073;178729072	chr2:179593801;179593800;179593799
N2AB	6005	18238;18239;18240	chr2:178729074;178729073;178729072	chr2:179593801;179593800;179593799
N2A	5078	15457;15458;15459	chr2:178729074;178729073;178729072	chr2:179593801;179593800;179593799
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-47
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4867
• 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
S/F	None	None	0.001	D	0.351	0.369	0.435043484731	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0881	likely_benign	0.086	benign	-0.627	Destabilizing	0.027	N	0.415	neutral	N	0.491786077	None	None	I
S/C	0.1502	likely_benign	0.1543	benign	-0.403	Destabilizing	0.915	D	0.513	neutral	D	0.546810085	None	None	I
S/D	0.3042	likely_benign	0.3246	benign	0.202	Stabilizing	0.149	N	0.433	neutral	None	None	None	None	I
S/E	0.3871	ambiguous	0.4172	ambiguous	0.217	Stabilizing	0.149	N	0.384	neutral	None	None	None	None	I
S/F	0.1394	likely_benign	0.1276	benign	-0.867	Destabilizing	0.001	N	0.351	neutral	D	0.523679401	None	None	I
S/G	0.1418	likely_benign	0.1357	benign	-0.877	Destabilizing	0.149	N	0.373	neutral	None	None	None	None	I
S/H	0.2564	likely_benign	0.2706	benign	-1.232	Destabilizing	0.935	D	0.519	neutral	None	None	None	None	I
S/I	0.1598	likely_benign	0.1525	benign	-0.071	Destabilizing	0.081	N	0.569	neutral	None	None	None	None	I
S/K	0.5234	ambiguous	0.5663	pathogenic	-0.443	Destabilizing	0.002	N	0.229	neutral	None	None	None	None	I
S/L	0.1034	likely_benign	0.1047	benign	-0.071	Destabilizing	0.001	N	0.383	neutral	None	None	None	None	I
S/M	0.1862	likely_benign	0.1883	benign	-0.035	Destabilizing	0.235	N	0.542	neutral	None	None	None	None	I
S/N	0.1312	likely_benign	0.1377	benign	-0.449	Destabilizing	0.149	N	0.451	neutral	None	None	None	None	I
S/P	0.6896	likely_pathogenic	0.7269	pathogenic	-0.222	Destabilizing	0.484	N	0.579	neutral	D	0.528198851	None	None	I
S/Q	0.3885	ambiguous	0.4173	ambiguous	-0.481	Destabilizing	0.38	N	0.469	neutral	None	None	None	None	I
S/R	0.4292	ambiguous	0.455	ambiguous	-0.415	Destabilizing	0.235	N	0.569	neutral	None	None	None	None	I
S/T	0.0681	likely_benign	0.0705	benign	-0.468	Destabilizing	0.002	N	0.236	neutral	N	0.472549803	None	None	I
S/V	0.1604	likely_benign	0.1619	benign	-0.222	Destabilizing	0.081	N	0.535	neutral	None	None	None	None	I
S/W	0.309	likely_benign	0.3038	benign	-0.898	Destabilizing	0.935	D	0.625	neutral	None	None	None	None	I
S/Y	0.1358	likely_benign	0.1312	benign	-0.588	Destabilizing	0.188	N	0.604	neutral	N	0.508448755	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.