TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29350	88273;88274;88275	chr2:178557106;178557105;178557104	chr2:179421833;179421832;179421831
N2AB	27709	83350;83351;83352	chr2:178557106;178557105;178557104	chr2:179421833;179421832;179421831
N2A	26782	80569;80570;80571	chr2:178557106;178557105;178557104	chr2:179421833;179421832;179421831
N2B	20285	61078;61079;61080	chr2:178557106;178557105;178557104	chr2:179421833;179421832;179421831
Novex-1	20410	61453;61454;61455	chr2:178557106;178557105;178557104	chr2:179421833;179421832;179421831
Novex-2	20477	61654;61655;61656	chr2:178557106;178557105;178557104	chr2:179421833;179421832;179421831
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-102
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3576
• 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/T	rs1218350204	None	0.001	N	0.069	0.091	0.184867976434	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/T	rs1218350204	None	0.001	N	0.069	0.091	0.184867976434	gnomAD-4.0.0	6.57298E-06	None	None	None	None	N	None	2.41231E-05	0	None	0	0	None	0	0	0	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	0.2714	likely_benign	0.2244	benign	-0.646	Destabilizing	0.116	N	0.341	neutral	None	None	None	None	N
N/C	0.3437	ambiguous	0.3067	benign	0.179	Stabilizing	0.944	D	0.399	neutral	None	None	None	None	N
N/D	0.1536	likely_benign	0.1332	benign	-0.559	Destabilizing	0.09	N	0.309	neutral	N	0.456200979	None	None	N
N/E	0.4328	ambiguous	0.36	ambiguous	-0.583	Destabilizing	0.002	N	0.125	neutral	None	None	None	None	N
N/F	0.5656	likely_pathogenic	0.451	ambiguous	-1.071	Destabilizing	0.818	D	0.421	neutral	None	None	None	None	N
N/G	0.3244	likely_benign	0.2903	benign	-0.815	Destabilizing	0.207	N	0.279	neutral	None	None	None	None	N
N/H	0.1326	likely_benign	0.1203	benign	-0.926	Destabilizing	0.773	D	0.375	neutral	N	0.471852991	None	None	N
N/I	0.3565	ambiguous	0.2902	benign	-0.276	Destabilizing	0.457	N	0.431	neutral	N	0.512011521	None	None	N
N/K	0.3925	ambiguous	0.3155	benign	0.059	Stabilizing	0.193	N	0.246	neutral	N	0.514153204	None	None	N
N/L	0.3357	likely_benign	0.277	benign	-0.276	Destabilizing	0.241	N	0.407	neutral	None	None	None	None	N
N/M	0.3496	ambiguous	0.294	benign	0.45	Stabilizing	0.944	D	0.371	neutral	None	None	None	None	N
N/P	0.8955	likely_pathogenic	0.8708	pathogenic	-0.375	Destabilizing	0.818	D	0.401	neutral	None	None	None	None	N
N/Q	0.3663	ambiguous	0.3118	benign	-0.676	Destabilizing	0.241	N	0.368	neutral	None	None	None	None	N
N/R	0.4504	ambiguous	0.3588	ambiguous	0.238	Stabilizing	0.388	N	0.361	neutral	None	None	None	None	N
N/S	0.0929	likely_benign	0.0914	benign	-0.303	Destabilizing	0.018	N	0.071	neutral	N	0.445194551	None	None	N
N/T	0.112	likely_benign	0.1005	benign	-0.19	Destabilizing	0.001	N	0.069	neutral	N	0.44018859	None	None	N
N/V	0.3394	likely_benign	0.2832	benign	-0.375	Destabilizing	0.241	N	0.401	neutral	None	None	None	None	N
N/W	0.804	likely_pathogenic	0.738	pathogenic	-0.948	Destabilizing	0.981	D	0.512	neutral	None	None	None	None	N
N/Y	0.1717	likely_benign	0.1443	benign	-0.682	Destabilizing	0.773	D	0.399	neutral	N	0.505263571	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.