TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29175	87748;87749;87750	chr2:178557831;178557830;178557829	chr2:179422558;179422557;179422556
N2AB	27534	82825;82826;82827	chr2:178557831;178557830;178557829	chr2:179422558;179422557;179422556
N2A	26607	80044;80045;80046	chr2:178557831;178557830;178557829	chr2:179422558;179422557;179422556
N2B	20110	60553;60554;60555	chr2:178557831;178557830;178557829	chr2:179422558;179422557;179422556
Novex-1	20235	60928;60929;60930	chr2:178557831;178557830;178557829	chr2:179422558;179422557;179422556
Novex-2	20302	61129;61130;61131	chr2:178557831;178557830;178557829	chr2:179422558;179422557;179422556
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-100
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0647
• 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
L/I	None	None	None	N	0.201	0.129	0.276898752692	gnomAD-4.0.0	1.36834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79886E-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
L/A	0.7064	likely_pathogenic	0.747	pathogenic	-2.992	Highly Destabilizing	0.007	N	0.546	neutral	None	None	None	None	N
L/C	0.7487	likely_pathogenic	0.7486	pathogenic	-2.32	Highly Destabilizing	0.356	N	0.712	prob.delet.	None	None	None	None	N
L/D	0.9978	likely_pathogenic	0.9981	pathogenic	-3.73	Highly Destabilizing	0.356	N	0.735	prob.delet.	None	None	None	None	N
L/E	0.9879	likely_pathogenic	0.9886	pathogenic	-3.409	Highly Destabilizing	0.136	N	0.686	prob.neutral	None	None	None	None	N
L/F	0.5011	ambiguous	0.5413	ambiguous	-1.843	Destabilizing	0.072	N	0.496	neutral	None	None	None	None	N
L/G	0.9496	likely_pathogenic	0.9616	pathogenic	-3.621	Highly Destabilizing	0.136	N	0.679	prob.neutral	None	None	None	None	N
L/H	0.9754	likely_pathogenic	0.9746	pathogenic	-3.239	Highly Destabilizing	0.864	D	0.807	deleterious	None	None	None	None	N
L/I	0.0538	likely_benign	0.0626	benign	-1.107	Destabilizing	None	N	0.201	neutral	N	0.363805319	None	None	N
L/K	0.9894	likely_pathogenic	0.9891	pathogenic	-2.558	Highly Destabilizing	0.136	N	0.655	neutral	None	None	None	None	N
L/M	0.2299	likely_benign	0.2491	benign	-1.169	Destabilizing	0.214	N	0.522	neutral	None	None	None	None	N
L/N	0.9846	likely_pathogenic	0.9842	pathogenic	-3.245	Highly Destabilizing	0.628	D	0.782	deleterious	None	None	None	None	N
L/P	0.9786	likely_pathogenic	0.9846	pathogenic	-1.725	Destabilizing	0.295	N	0.745	deleterious	D	0.528856085	None	None	N
L/Q	0.9645	likely_pathogenic	0.9657	pathogenic	-2.919	Highly Destabilizing	0.56	D	0.774	deleterious	N	0.483390789	None	None	N
L/R	0.9754	likely_pathogenic	0.9763	pathogenic	-2.466	Highly Destabilizing	0.295	N	0.765	deleterious	N	0.483390789	None	None	N
L/S	0.9424	likely_pathogenic	0.9457	pathogenic	-3.867	Highly Destabilizing	0.072	N	0.619	neutral	None	None	None	None	N
L/T	0.7832	likely_pathogenic	0.7944	pathogenic	-3.376	Highly Destabilizing	0.016	N	0.519	neutral	None	None	None	None	N
L/V	0.0498	likely_benign	0.06	benign	-1.725	Destabilizing	None	N	0.175	neutral	N	0.306330309	None	None	N
L/W	0.9485	likely_pathogenic	0.9462	pathogenic	-2.294	Highly Destabilizing	0.864	D	0.789	deleterious	None	None	None	None	N
L/Y	0.9405	likely_pathogenic	0.9406	pathogenic	-2.056	Highly Destabilizing	0.356	N	0.639	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.