TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9378	28357;28358;28359	chr2:178711104;178711103;178711102	chr2:179575831;179575830;179575829
N2AB	9061	27406;27407;27408	chr2:178711104;178711103;178711102	chr2:179575831;179575830;179575829
N2A	8134	24625;24626;24627	chr2:178711104;178711103;178711102	chr2:179575831;179575830;179575829
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-79
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.7286
• 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
P/S	rs879082824	None	0.01	None	0.081	0.162	0.159798565429	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs879082824	None	0.01	None	0.081	0.162	0.159798565429	gnomAD-4.0.0	6.20008E-06	None	None	None	None	I	None	1.33526E-05	0	None	0	0	None	0	0	7.63137E-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
P/A	0.0685	likely_benign	0.0751	benign	-0.427	Destabilizing	0.002	N	0.09	neutral	None	None	None	None	I
P/C	0.4672	ambiguous	0.5872	pathogenic	-0.731	Destabilizing	0.944	D	0.255	neutral	None	None	None	None	I
P/D	0.2174	likely_benign	0.3228	benign	-0.4	Destabilizing	0.003	N	0.095	neutral	None	None	None	None	I
P/E	0.164	likely_benign	0.2226	benign	-0.516	Destabilizing	0.013	N	0.105	neutral	None	None	None	None	I
P/F	0.2684	likely_benign	0.3661	ambiguous	-0.694	Destabilizing	0.007	N	0.209	neutral	None	None	None	None	I
P/G	0.2156	likely_benign	0.2772	benign	-0.529	Destabilizing	0.003	N	0.097	neutral	None	None	None	None	I
P/H	0.1186	likely_benign	0.1654	benign	-0.069	Destabilizing	0.975	D	0.273	neutral	None	None	None	None	I
P/I	0.1835	likely_benign	0.251	benign	-0.307	Destabilizing	0.543	D	0.325	neutral	None	None	None	None	I
P/K	0.1981	likely_benign	0.252	benign	-0.475	Destabilizing	0.495	N	0.306	neutral	None	None	None	None	I
P/L	0.1064	likely_benign	0.1362	benign	-0.307	Destabilizing	0.27	N	0.326	neutral	None	None	None	None	I
P/M	0.2243	likely_benign	0.2835	benign	-0.47	Destabilizing	0.944	D	0.274	neutral	None	None	None	None	I
P/N	0.1798	likely_benign	0.268	benign	-0.27	Destabilizing	0.495	N	0.3	neutral	None	None	None	None	I
P/Q	0.1152	likely_benign	0.1498	benign	-0.506	Destabilizing	0.704	D	0.288	neutral	None	None	None	None	I
P/R	0.1281	likely_benign	0.1568	benign	0.052	Stabilizing	0.642	D	0.32	neutral	None	None	None	None	I
P/S	0.0874	likely_benign	0.1083	benign	-0.587	Destabilizing	0.01	N	0.081	neutral	None	None	None	None	I
P/T	0.0783	likely_benign	0.0965	benign	-0.607	Destabilizing	0.27	N	0.273	neutral	None	None	None	None	I
P/V	0.1428	likely_benign	0.181	benign	-0.315	Destabilizing	0.329	N	0.277	neutral	None	None	None	None	I
P/W	0.4557	ambiguous	0.5955	pathogenic	-0.765	Destabilizing	0.995	D	0.257	neutral	None	None	None	None	I
P/Y	0.2481	likely_benign	0.3506	ambiguous	-0.481	Destabilizing	0.543	D	0.317	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.