TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6550	19873;19874;19875	chr2:178728176;178728175;178728174	chr2:179592903;179592902;179592901
N2AB	6233	18922;18923;18924	chr2:178728176;178728175;178728174	chr2:179592903;179592902;179592901
N2A	5306	16141;16142;16143	chr2:178728176;178728175;178728174	chr2:179592903;179592902;179592901
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-49
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3918
• 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
N/D	rs1333479032	None	0.003	N	0.179	0.08	0.17258766438	gnomAD-4.0.0	4.11047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.4014E-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
N/A	0.2162	likely_benign	0.2226	benign	-0.976	Destabilizing	0.209	N	0.393	neutral	None	None	None	None	N
N/C	0.3911	ambiguous	0.3974	ambiguous	-0.056	Destabilizing	0.991	D	0.543	neutral	None	None	None	None	N
N/D	0.1741	likely_benign	0.1736	benign	-0.663	Destabilizing	0.003	N	0.179	neutral	N	0.471432295	None	None	N
N/E	0.3942	ambiguous	0.4101	ambiguous	-0.612	Destabilizing	0.209	N	0.375	neutral	None	None	None	None	N
N/F	0.5102	ambiguous	0.5218	ambiguous	-1.046	Destabilizing	0.901	D	0.551	neutral	None	None	None	None	N
N/G	0.3546	ambiguous	0.367	ambiguous	-1.25	Destabilizing	0.345	N	0.382	neutral	None	None	None	None	N
N/H	0.1261	likely_benign	0.1312	benign	-1.112	Destabilizing	0.007	N	0.269	neutral	D	0.536406494	None	None	N
N/I	0.1737	likely_benign	0.1891	benign	-0.298	Destabilizing	0.772	D	0.57	neutral	N	0.489844698	None	None	N
N/K	0.3313	likely_benign	0.3472	ambiguous	-0.149	Destabilizing	0.166	N	0.375	neutral	N	0.467466483	None	None	N
N/L	0.2289	likely_benign	0.2341	benign	-0.298	Destabilizing	0.561	D	0.49	neutral	None	None	None	None	N
N/M	0.3364	likely_benign	0.3561	ambiguous	0.374	Stabilizing	0.965	D	0.534	neutral	None	None	None	None	N
N/P	0.6645	likely_pathogenic	0.7113	pathogenic	-0.497	Destabilizing	0.901	D	0.573	neutral	None	None	None	None	N
N/Q	0.3672	ambiguous	0.3819	ambiguous	-0.909	Destabilizing	0.561	D	0.433	neutral	None	None	None	None	N
N/R	0.3375	likely_benign	0.3513	ambiguous	-0.052	Destabilizing	0.004	N	0.285	neutral	None	None	None	None	N
N/S	0.0824	likely_benign	0.0817	benign	-0.762	Destabilizing	0.036	N	0.177	neutral	N	0.470738862	None	None	N
N/T	0.1223	likely_benign	0.1316	benign	-0.53	Destabilizing	0.005	N	0.144	neutral	N	0.406266096	None	None	N
N/V	0.1762	likely_benign	0.1899	benign	-0.497	Destabilizing	0.561	D	0.486	neutral	None	None	None	None	N
N/W	0.7893	likely_pathogenic	0.8067	pathogenic	-0.798	Destabilizing	0.991	D	0.568	neutral	None	None	None	None	N
N/Y	0.1676	likely_benign	0.1703	benign	-0.58	Destabilizing	0.629	D	0.558	neutral	N	0.510721402	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.