TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6319	19180;19181;19182	chr2:178729083;178729082;178729081	chr2:179593810;179593809;179593808
N2AB	6002	18229;18230;18231	chr2:178729083;178729082;178729081	chr2:179593810;179593809;179593808
N2A	5075	15448;15449;15450	chr2:178729083;178729082;178729081	chr2:179593810;179593809;179593808
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-47
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.5849
• 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/L	rs2079901596	None	0.032	D	0.321	0.517	0.638853250657	gnomAD-4.0.0	1.59475E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02994E-05
P/S	rs749058126	-0.086	0.942	D	0.4	0.558	0.487772906946	gnomAD-2.1.1	8.17E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.81E-05	0
P/S	rs749058126	-0.086	0.942	D	0.4	0.558	0.487772906946	gnomAD-4.0.0	2.05466E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.60982E-05	0	1.65837E-05

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	0.0762	likely_benign	0.0698	benign	-0.394	Destabilizing	0.822	D	0.425	neutral	N	0.499243086	None	None	I
P/C	0.4253	ambiguous	0.4032	ambiguous	-0.803	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	I
P/D	0.3251	likely_benign	0.2823	benign	-0.423	Destabilizing	0.956	D	0.405	neutral	None	None	None	None	I
P/E	0.179	likely_benign	0.167	benign	-0.538	Destabilizing	0.754	D	0.441	neutral	None	None	None	None	I
P/F	0.265	likely_benign	0.2337	benign	-0.746	Destabilizing	0.915	D	0.581	neutral	None	None	None	None	I
P/G	0.275	likely_benign	0.2452	benign	-0.46	Destabilizing	0.956	D	0.417	neutral	None	None	None	None	I
P/H	0.1088	likely_benign	0.0986	benign	-0.033	Destabilizing	0.992	D	0.479	neutral	D	0.593669589	None	None	I
P/I	0.2086	likely_benign	0.1841	benign	-0.362	Destabilizing	0.915	D	0.558	neutral	None	None	None	None	I
P/K	0.1621	likely_benign	0.1521	benign	-0.46	Destabilizing	0.915	D	0.401	neutral	None	None	None	None	I
P/L	0.0784	likely_benign	0.0736	benign	-0.362	Destabilizing	0.032	N	0.321	neutral	D	0.550254799	None	None	I
P/M	0.2222	likely_benign	0.1983	benign	-0.613	Destabilizing	0.988	D	0.487	neutral	None	None	None	None	I
P/N	0.2352	likely_benign	0.2046	benign	-0.263	Destabilizing	0.956	D	0.492	neutral	None	None	None	None	I
P/Q	0.0947	likely_benign	0.0883	benign	-0.478	Destabilizing	0.16	N	0.317	neutral	None	None	None	None	I
P/R	0.1106	likely_benign	0.1068	benign	0.01	Stabilizing	0.89	D	0.501	neutral	D	0.58026476	None	None	I
P/S	0.0919	likely_benign	0.0846	benign	-0.559	Destabilizing	0.942	D	0.4	neutral	D	0.530171678	None	None	I
P/T	0.098	likely_benign	0.0876	benign	-0.583	Destabilizing	0.942	D	0.405	neutral	D	0.54985119	None	None	I
P/V	0.1586	likely_benign	0.1424	benign	-0.344	Destabilizing	0.754	D	0.427	neutral	None	None	None	None	I
P/W	0.4495	ambiguous	0.41	ambiguous	-0.804	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	I
P/Y	0.2473	likely_benign	0.2275	benign	-0.535	Destabilizing	0.978	D	0.583	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.