TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7533	22822;22823;22824	chr2:178722066;178722065;178722064	chr2:179586793;179586792;179586791
N2AB	7216	21871;21872;21873	chr2:178722066;178722065;178722064	chr2:179586793;179586792;179586791
N2A	6289	19090;19091;19092	chr2:178722066;178722065;178722064	chr2:179586793;179586792;179586791
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-60
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4293
• 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
D/N	rs371762361	-0.522	0.324	N	0.518	0.179	None	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
D/N	rs371762361	-0.522	0.324	N	0.518	0.179	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs371762361	-0.522	0.324	N	0.518	0.179	None	gnomAD-4.0.0	6.57151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47016E-05	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
D/A	0.2713	likely_benign	0.2925	benign	-0.36	Destabilizing	0.09	N	0.479	neutral	N	0.419439597	None	None	N
D/C	0.8422	likely_pathogenic	0.8383	pathogenic	-0.224	Destabilizing	0.981	D	0.617	neutral	None	None	None	None	N
D/E	0.2813	likely_benign	0.3229	benign	-0.62	Destabilizing	0.003	N	0.279	neutral	N	0.352041169	None	None	N
D/F	0.6932	likely_pathogenic	0.7404	pathogenic	0.25	Stabilizing	0.932	D	0.603	neutral	None	None	None	None	N
D/G	0.3795	ambiguous	0.43	ambiguous	-0.739	Destabilizing	0.001	N	0.353	neutral	N	0.496630944	None	None	N
D/H	0.4052	ambiguous	0.4537	ambiguous	-0.021	Destabilizing	0.912	D	0.561	neutral	N	0.364125032	None	None	N
D/I	0.4078	ambiguous	0.4348	ambiguous	0.647	Stabilizing	0.818	D	0.6	neutral	None	None	None	None	N
D/K	0.6081	likely_pathogenic	0.663	pathogenic	-0.349	Destabilizing	0.388	N	0.463	neutral	None	None	None	None	N
D/L	0.4846	ambiguous	0.5441	ambiguous	0.647	Stabilizing	0.818	D	0.589	neutral	None	None	None	None	N
D/M	0.7127	likely_pathogenic	0.7531	pathogenic	0.968	Stabilizing	0.981	D	0.599	neutral	None	None	None	None	N
D/N	0.1293	likely_benign	0.1393	benign	-0.888	Destabilizing	0.324	N	0.518	neutral	N	0.412705626	None	None	N
D/P	0.934	likely_pathogenic	0.9561	pathogenic	0.338	Stabilizing	0.818	D	0.564	neutral	None	None	None	None	N
D/Q	0.5065	ambiguous	0.5786	pathogenic	-0.69	Destabilizing	0.69	D	0.531	neutral	None	None	None	None	N
D/R	0.5814	likely_pathogenic	0.6461	pathogenic	-0.107	Destabilizing	0.69	D	0.579	neutral	None	None	None	None	N
D/S	0.1677	likely_benign	0.1891	benign	-1.128	Destabilizing	0.024	N	0.419	neutral	None	None	None	None	N
D/T	0.2983	likely_benign	0.331	benign	-0.808	Destabilizing	0.241	N	0.459	neutral	None	None	None	None	N
D/V	0.2441	likely_benign	0.2585	benign	0.338	Stabilizing	0.773	D	0.59	neutral	N	0.379822416	None	None	N
D/W	0.9342	likely_pathogenic	0.9485	pathogenic	0.442	Stabilizing	0.981	D	0.618	neutral	None	None	None	None	N
D/Y	0.3262	likely_benign	0.3485	ambiguous	0.493	Stabilizing	0.912	D	0.603	neutral	N	0.434158333	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.