TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20819	62680;62681;62682	chr2:178589270;178589269;178589268	chr2:179453997;179453996;179453995
N2AB	19178	57757;57758;57759	chr2:178589270;178589269;178589268	chr2:179453997;179453996;179453995
N2A	18251	54976;54977;54978	chr2:178589270;178589269;178589268	chr2:179453997;179453996;179453995
N2B	11754	35485;35486;35487	chr2:178589270;178589269;178589268	chr2:179453997;179453996;179453995
Novex-1	11879	35860;35861;35862	chr2:178589270;178589269;178589268	chr2:179453997;179453996;179453995
Novex-2	11946	36061;36062;36063	chr2:178589270;178589269;178589268	chr2:179453997;179453996;179453995
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-122
• Domain position: 51
• Structural Position: 122
• Q(SASA): 0.6001
• 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/E	rs561142365	0.684	0.334	N	0.431	0.251	0.247872288689	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.23514E-04	None	0	None	0	0	0
K/E	rs561142365	0.684	0.334	N	0.431	0.251	0.247872288689	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	3.88199E-04	None	0	0	0	0	0
K/E	rs561142365	0.684	0.334	N	0.431	0.251	0.247872288689	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
K/E	rs561142365	0.684	0.334	N	0.431	0.251	0.247872288689	gnomAD-4.0.0	4.95825E-06	None	None	None	None	N	None	0	0	None	0	1.78707E-04	None	0	0	0	0	0
K/N	rs2049719955	None	0.004	N	0.173	0.076	0.141422826196	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs2049719955	None	0.004	N	0.173	0.076	0.141422826196	gnomAD-4.0.0	1.85953E-06	None	None	None	None	N	None	4.00545E-05	0	None	0	0	None	0	0	0	0	0
K/R	rs780962150	None	0.549	N	0.421	0.107	0.299770980665	gnomAD-4.0.0	1.71084E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.24893E-05	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
K/A	0.2361	likely_benign	0.2088	benign	-0.009	Destabilizing	0.25	N	0.402	neutral	None	None	None	None	N
K/C	0.5195	ambiguous	0.508	ambiguous	-0.389	Destabilizing	0.992	D	0.509	neutral	None	None	None	None	N
K/D	0.4865	ambiguous	0.4464	ambiguous	0.094	Stabilizing	0.447	N	0.464	neutral	None	None	None	None	N
K/E	0.182	likely_benign	0.1685	benign	0.118	Stabilizing	0.334	N	0.431	neutral	N	0.454425402	None	None	N
K/F	0.6196	likely_pathogenic	0.5655	pathogenic	-0.166	Destabilizing	0.92	D	0.524	neutral	None	None	None	None	N
K/G	0.4194	ambiguous	0.3706	ambiguous	-0.22	Destabilizing	0.25	N	0.447	neutral	None	None	None	None	N
K/H	0.1871	likely_benign	0.1725	benign	-0.409	Destabilizing	0.85	D	0.511	neutral	None	None	None	None	N
K/I	0.2336	likely_benign	0.2147	benign	0.469	Stabilizing	0.85	D	0.511	neutral	None	None	None	None	N
K/L	0.2783	likely_benign	0.2561	benign	0.469	Stabilizing	0.447	N	0.489	neutral	None	None	None	None	N
K/M	0.1694	likely_benign	0.1534	benign	0.112	Stabilizing	0.963	D	0.51	neutral	D	0.522959981	None	None	N
K/N	0.2983	likely_benign	0.2594	benign	0.023	Stabilizing	0.004	N	0.173	neutral	N	0.46439168	None	None	N
K/P	0.9238	likely_pathogenic	0.9194	pathogenic	0.338	Stabilizing	0.92	D	0.526	neutral	None	None	None	None	N
K/Q	0.0992	likely_benign	0.0911	benign	-0.089	Destabilizing	0.549	D	0.457	neutral	N	0.46402632	None	None	N
K/R	0.0828	likely_benign	0.082	benign	-0.107	Destabilizing	0.549	D	0.421	neutral	N	0.434858207	None	None	N
K/S	0.2558	likely_benign	0.231	benign	-0.458	Destabilizing	0.003	N	0.137	neutral	None	None	None	None	N
K/T	0.0981	likely_benign	0.0913	benign	-0.277	Destabilizing	0.016	N	0.246	neutral	N	0.422334413	None	None	N
K/V	0.2029	likely_benign	0.1918	benign	0.338	Stabilizing	0.447	N	0.482	neutral	None	None	None	None	N
K/W	0.692	likely_pathogenic	0.6316	pathogenic	-0.198	Destabilizing	0.992	D	0.565	neutral	None	None	None	None	N
K/Y	0.5185	ambiguous	0.4775	ambiguous	0.156	Stabilizing	0.972	D	0.513	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.