TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3139	9640;9641;9642	chr2:178767815;178767814;178767813	chr2:179632542;179632541;179632540
N2AB	3139	9640;9641;9642	chr2:178767815;178767814;178767813	chr2:179632542;179632541;179632540
N2A	3139	9640;9641;9642	chr2:178767815;178767814;178767813	chr2:179632542;179632541;179632540
N2B	3093	9502;9503;9504	chr2:178767815;178767814;178767813	chr2:179632542;179632541;179632540
Novex-1	3093	9502;9503;9504	chr2:178767815;178767814;178767813	chr2:179632542;179632541;179632540
Novex-2	3093	9502;9503;9504	chr2:178767815;178767814;178767813	chr2:179632542;179632541;179632540
Novex-3	3139	9640;9641;9642	chr2:178767815;178767814;178767813	chr2:179632542;179632541;179632540

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-21
• Domain position: 82
• Structural Position: 173
• Q(SASA): 0.5693
• 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	rs1346392116	-0.06	None	N	0.116	0.063	0.0138822411134	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
K/N	rs1346392116	-0.06	None	N	0.116	0.063	0.0138822411134	gnomAD-4.0.0	1.36815E-06	None	None	None	None	N	None	0	4.47207E-05	None	0	0	None	0	0	0	0	0
K/Q	None	None	None	N	0.1	0.124	0.0482279557977	gnomAD-4.0.0	1.59052E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.1577	likely_benign	0.145	benign	-0.768	Destabilizing	0.002	N	0.253	neutral	None	None	None	None	N
K/C	0.3916	ambiguous	0.3243	benign	-0.624	Destabilizing	0.497	N	0.483	neutral	None	None	None	None	N
K/D	0.1965	likely_benign	0.1531	benign	0.219	Stabilizing	0.004	N	0.271	neutral	None	None	None	None	N
K/E	0.1173	likely_benign	0.1198	benign	0.35	Stabilizing	0.003	N	0.24	neutral	N	0.346911607	None	None	N
K/F	0.4728	ambiguous	0.4641	ambiguous	-0.396	Destabilizing	0.085	N	0.571	neutral	None	None	None	None	N
K/G	0.2606	likely_benign	0.2591	benign	-1.138	Destabilizing	0.004	N	0.281	neutral	None	None	None	None	N
K/H	0.1065	likely_benign	0.0865	benign	-1.296	Destabilizing	None	N	0.201	neutral	None	None	None	None	N
K/I	0.1779	likely_benign	0.1791	benign	0.197	Stabilizing	0.033	N	0.552	neutral	N	0.309765095	None	None	N
K/L	0.191	likely_benign	0.1844	benign	0.197	Stabilizing	0.018	N	0.313	neutral	None	None	None	None	N
K/M	0.1281	likely_benign	0.1406	benign	0.038	Stabilizing	0.497	N	0.477	neutral	None	None	None	None	N
K/N	0.0754	likely_benign	0.0568	benign	-0.365	Destabilizing	None	N	0.116	neutral	N	0.343810882	None	None	N
K/P	0.7797	likely_pathogenic	0.7485	pathogenic	-0.096	Destabilizing	0.037	N	0.497	neutral	None	None	None	None	N
K/Q	0.088	likely_benign	0.0862	benign	-0.388	Destabilizing	None	N	0.1	neutral	N	0.349072024	None	None	N
K/R	0.0765	likely_benign	0.0755	benign	-0.431	Destabilizing	0.014	N	0.275	neutral	N	0.348012771	None	None	N
K/S	0.1086	likely_benign	0.0867	benign	-1.134	Destabilizing	None	N	0.111	neutral	None	None	None	None	N
K/T	0.0675	likely_benign	0.0679	benign	-0.782	Destabilizing	None	N	0.181	neutral	N	0.347248593	None	None	N
K/V	0.1617	likely_benign	0.1591	benign	-0.096	Destabilizing	0.018	N	0.373	neutral	None	None	None	None	N
K/W	0.5757	likely_pathogenic	0.582	pathogenic	-0.22	Destabilizing	0.788	D	0.47	neutral	None	None	None	None	N
K/Y	0.247	likely_benign	0.2147	benign	0.043	Stabilizing	0.044	N	0.538	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.