TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7969	24130;24131;24132	chr2:178719587;178719586;178719585	chr2:179584314;179584313;179584312
N2AB	7652	23179;23180;23181	chr2:178719587;178719586;178719585	chr2:179584314;179584313;179584312
N2A	6725	20398;20399;20400	chr2:178719587;178719586;178719585	chr2:179584314;179584313;179584312
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-64
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6175
• 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
K/N	rs1454384580	0.412	0.213	D	0.367	0.101	0.15556083564	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	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
K/A	0.2559	likely_benign	0.2298	benign	-0.036	Destabilizing	0.129	N	0.468	neutral	None	None	None	None	N
K/C	0.6192	likely_pathogenic	0.5655	pathogenic	-0.193	Destabilizing	0.983	D	0.535	neutral	None	None	None	None	N
K/D	0.4056	ambiguous	0.3507	ambiguous	0.133	Stabilizing	0.002	N	0.233	neutral	None	None	None	None	N
K/E	0.1054	likely_benign	0.0983	benign	0.144	Stabilizing	0.002	N	0.137	neutral	N	0.459753864	None	None	N
K/F	0.5966	likely_pathogenic	0.5459	ambiguous	-0.208	Destabilizing	0.94	D	0.541	neutral	None	None	None	None	N
K/G	0.3818	ambiguous	0.3317	benign	-0.253	Destabilizing	0.228	N	0.514	neutral	None	None	None	None	N
K/H	0.2548	likely_benign	0.2152	benign	-0.547	Destabilizing	0.716	D	0.511	neutral	None	None	None	None	N
K/I	0.24	likely_benign	0.2268	benign	0.46	Stabilizing	0.794	D	0.549	neutral	N	0.497043224	None	None	N
K/L	0.2872	likely_benign	0.2659	benign	0.46	Stabilizing	0.418	N	0.527	neutral	None	None	None	None	N
K/M	0.1568	likely_benign	0.1572	benign	0.318	Stabilizing	0.836	D	0.509	neutral	None	None	None	None	N
K/N	0.2577	likely_benign	0.2265	benign	0.27	Stabilizing	0.213	N	0.367	neutral	D	0.532811615	None	None	N
K/P	0.8403	likely_pathogenic	0.7936	pathogenic	0.324	Stabilizing	0.593	D	0.5	neutral	None	None	None	None	N
K/Q	0.1003	likely_benign	0.0959	benign	0.06	Stabilizing	0.007	N	0.213	neutral	D	0.525325495	None	None	N
K/R	0.0863	likely_benign	0.0807	benign	0.007	Stabilizing	0.001	N	0.132	neutral	N	0.512801702	None	None	N
K/S	0.247	likely_benign	0.2157	benign	-0.276	Destabilizing	0.027	N	0.156	neutral	None	None	None	None	N
K/T	0.1131	likely_benign	0.1081	benign	-0.11	Destabilizing	0.351	N	0.459	neutral	N	0.521517186	None	None	N
K/V	0.2301	likely_benign	0.2101	benign	0.324	Stabilizing	0.418	N	0.532	neutral	None	None	None	None	N
K/W	0.6706	likely_pathogenic	0.6081	pathogenic	-0.174	Destabilizing	0.983	D	0.573	neutral	None	None	None	None	N
K/Y	0.475	ambiguous	0.4189	ambiguous	0.177	Stabilizing	0.836	D	0.529	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.