TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23201	69826;69827;69828	chr2:178576643;178576642;178576641	chr2:179441370;179441369;179441368
N2AB	21560	64903;64904;64905	chr2:178576643;178576642;178576641	chr2:179441370;179441369;179441368
N2A	20633	62122;62123;62124	chr2:178576643;178576642;178576641	chr2:179441370;179441369;179441368
N2B	14136	42631;42632;42633	chr2:178576643;178576642;178576641	chr2:179441370;179441369;179441368
Novex-1	14261	43006;43007;43008	chr2:178576643;178576642;178576641	chr2:179441370;179441369;179441368
Novex-2	14328	43207;43208;43209	chr2:178576643;178576642;178576641	chr2:179441370;179441369;179441368
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-56
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1463
• 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
V/I	None	None	0.767	N	0.235	0.154	0.42805410278	gnomAD-4.0.0	1.36855E-06	None	None	None	None	N	None	5.97907E-05	0	None	0	0	None	0	0	0	0	0
V/L	None	None	0.981	N	0.604	0.269	0.380901646489	gnomAD-4.0.0	6.84274E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15945E-05	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
V/A	0.6352	likely_pathogenic	0.6722	pathogenic	-1.953	Destabilizing	0.998	D	0.602	neutral	D	0.526663929	None	None	N
V/C	0.9282	likely_pathogenic	0.9352	pathogenic	-1.561	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/D	0.9863	likely_pathogenic	0.9915	pathogenic	-1.755	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/E	0.9594	likely_pathogenic	0.9715	pathogenic	-1.629	Destabilizing	1.0	D	0.819	deleterious	D	0.533566178	None	None	N
V/F	0.5789	likely_pathogenic	0.6238	pathogenic	-1.277	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/G	0.8475	likely_pathogenic	0.88	pathogenic	-2.424	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.533566178	None	None	N
V/H	0.9863	likely_pathogenic	0.9904	pathogenic	-1.959	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/I	0.0928	likely_benign	0.0927	benign	-0.695	Destabilizing	0.767	D	0.235	neutral	N	0.482792934	None	None	N
V/K	0.9791	likely_pathogenic	0.9845	pathogenic	-1.633	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/L	0.4537	ambiguous	0.472	ambiguous	-0.695	Destabilizing	0.981	D	0.604	neutral	N	0.501951911	None	None	N
V/M	0.4358	ambiguous	0.4669	ambiguous	-0.653	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
V/N	0.9573	likely_pathogenic	0.9714	pathogenic	-1.653	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/P	0.9802	likely_pathogenic	0.9849	pathogenic	-1.082	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/Q	0.9625	likely_pathogenic	0.9714	pathogenic	-1.628	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/R	0.971	likely_pathogenic	0.9786	pathogenic	-1.301	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/S	0.8874	likely_pathogenic	0.9135	pathogenic	-2.347	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/T	0.7963	likely_pathogenic	0.8278	pathogenic	-2.073	Highly Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
V/W	0.9885	likely_pathogenic	0.9912	pathogenic	-1.573	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/Y	0.9396	likely_pathogenic	0.9509	pathogenic	-1.253	Destabilizing	1.0	D	0.786	deleterious	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.