TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6987	21184;21185;21186	chr2:178724416;178724415;178724414	chr2:179589143;179589142;179589141
N2AB	6670	20233;20234;20235	chr2:178724416;178724415;178724414	chr2:179589143;179589142;179589141
N2A	5743	17452;17453;17454	chr2:178724416;178724415;178724414	chr2:179589143;179589142;179589141
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-54
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.3334
• 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
L/P	rs375676942	-0.637	0.966	N	0.409	0.307	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.6533E-04	0	None	0	0	None	0	None	0	0	0
L/P	rs375676942	-0.637	0.966	N	0.409	0.307	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	1.44725E-04	0	0	0	0	None	0	0	0	0	0
L/P	rs375676942	-0.637	0.966	N	0.409	0.307	None	gnomAD-4.0.0	3.94348E-05	None	None	None	None	N	None	1.44725E-04	0	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
L/A	0.1398	likely_benign	0.1275	benign	-1.075	Destabilizing	0.688	D	0.293	neutral	None	None	None	None	N
L/C	0.3477	ambiguous	0.3462	ambiguous	-0.702	Destabilizing	0.998	D	0.392	neutral	None	None	None	None	N
L/D	0.5469	ambiguous	0.5454	ambiguous	-0.202	Destabilizing	0.525	D	0.329	neutral	None	None	None	None	N
L/E	0.177	likely_benign	0.1689	benign	-0.204	Destabilizing	0.002	N	0.238	neutral	None	None	None	None	N
L/F	0.1523	likely_benign	0.1528	benign	-0.651	Destabilizing	0.991	D	0.366	neutral	None	None	None	None	N
L/G	0.3854	ambiguous	0.3729	ambiguous	-1.353	Destabilizing	0.842	D	0.347	neutral	None	None	None	None	N
L/H	0.1498	likely_benign	0.1489	benign	-0.437	Destabilizing	0.974	D	0.431	neutral	None	None	None	None	N
L/I	0.0798	likely_benign	0.0782	benign	-0.41	Destabilizing	0.915	D	0.281	neutral	None	None	None	None	N
L/K	0.091	likely_benign	0.0839	benign	-0.609	Destabilizing	0.525	D	0.304	neutral	None	None	None	None	N
L/M	0.0937	likely_benign	0.0886	benign	-0.481	Destabilizing	0.989	D	0.415	neutral	N	0.484478242	None	None	N
L/N	0.2857	likely_benign	0.2707	benign	-0.509	Destabilizing	0.842	D	0.375	neutral	None	None	None	None	N
L/P	0.0886	likely_benign	0.0863	benign	-0.599	Destabilizing	0.966	D	0.409	neutral	N	0.464754252	None	None	N
L/Q	0.076	likely_benign	0.072	benign	-0.622	Destabilizing	0.669	D	0.321	neutral	N	0.518511379	None	None	N
L/R	0.0834	likely_benign	0.0771	benign	-0.109	Destabilizing	0.801	D	0.34	neutral	N	0.507718382	None	None	N
L/S	0.2093	likely_benign	0.2065	benign	-1.106	Destabilizing	0.842	D	0.311	neutral	None	None	None	None	N
L/T	0.1578	likely_benign	0.1547	benign	-0.987	Destabilizing	0.842	D	0.27	neutral	None	None	None	None	N
L/V	0.0776	likely_benign	0.0749	benign	-0.599	Destabilizing	0.771	D	0.309	neutral	N	0.518300735	None	None	N
L/W	0.2121	likely_benign	0.2189	benign	-0.711	Destabilizing	0.998	D	0.469	neutral	None	None	None	None	N
L/Y	0.2754	likely_benign	0.27	benign	-0.466	Destabilizing	0.991	D	0.374	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.