TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7993	24202;24203;24204	chr2:178719413;178719412;178719411	chr2:179584140;179584139;179584138
N2AB	7676	23251;23252;23253	chr2:178719413;178719412;178719411	chr2:179584140;179584139;179584138
N2A	6749	20470;20471;20472	chr2:178719413;178719412;178719411	chr2:179584140;179584139;179584138
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: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-65
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5983
• 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/E	rs751011918	-0.1	0.004	N	0.069	0.123	0.0954503805726	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
D/E	rs751011918	-0.1	0.004	N	0.069	0.123	0.0954503805726	gnomAD-4.0.0	1.36886E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31911E-05	0
D/G	None	None	0.379	N	0.301	0.235	0.168933306366	gnomAD-4.0.0	1.59251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86189E-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
D/A	0.136	likely_benign	0.1576	benign	-0.176	Destabilizing	0.379	N	0.339	neutral	N	0.47207853	None	None	N
D/C	0.639	likely_pathogenic	0.6996	pathogenic	0.027	Stabilizing	0.992	D	0.474	neutral	None	None	None	None	N
D/E	0.1356	likely_benign	0.1532	benign	-0.346	Destabilizing	0.004	N	0.069	neutral	N	0.452805596	None	None	N
D/F	0.5903	likely_pathogenic	0.659	pathogenic	-0.179	Destabilizing	0.92	D	0.45	neutral	None	None	None	None	N
D/G	0.1303	likely_benign	0.1503	benign	-0.363	Destabilizing	0.379	N	0.301	neutral	N	0.474115992	None	None	N
D/H	0.256	likely_benign	0.2881	benign	0.023	Stabilizing	0.81	D	0.403	neutral	N	0.478928612	None	None	N
D/I	0.3636	ambiguous	0.4324	ambiguous	0.262	Stabilizing	0.739	D	0.451	neutral	None	None	None	None	N
D/K	0.3058	likely_benign	0.3415	ambiguous	0.311	Stabilizing	0.447	N	0.287	neutral	None	None	None	None	N
D/L	0.3824	ambiguous	0.446	ambiguous	0.262	Stabilizing	0.739	D	0.405	neutral	None	None	None	None	N
D/M	0.5442	ambiguous	0.6175	pathogenic	0.306	Stabilizing	0.977	D	0.433	neutral	None	None	None	None	N
D/N	0.0854	likely_benign	0.0926	benign	0.051	Stabilizing	0.004	N	0.225	neutral	N	0.488051533	None	None	N
D/P	0.3711	ambiguous	0.3943	ambiguous	0.138	Stabilizing	0.92	D	0.387	neutral	None	None	None	None	N
D/Q	0.3034	likely_benign	0.3466	ambiguous	0.077	Stabilizing	0.739	D	0.327	neutral	None	None	None	None	N
D/R	0.3457	ambiguous	0.3818	ambiguous	0.483	Stabilizing	0.85	D	0.397	neutral	None	None	None	None	N
D/S	0.1221	likely_benign	0.1365	benign	-0.046	Destabilizing	0.25	N	0.273	neutral	None	None	None	None	N
D/T	0.2019	likely_benign	0.2297	benign	0.095	Stabilizing	0.005	N	0.219	neutral	None	None	None	None	N
D/V	0.204	likely_benign	0.2434	benign	0.138	Stabilizing	0.379	N	0.41	neutral	N	0.476522302	None	None	N
D/W	0.8505	likely_pathogenic	0.884	pathogenic	-0.088	Destabilizing	0.992	D	0.578	neutral	None	None	None	None	N
D/Y	0.2081	likely_benign	0.2432	benign	0.049	Stabilizing	0.896	D	0.45	neutral	N	0.492259927	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.