TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1576	4951;4952;4953	chr2:178777237;178777236;178777235	chr2:179641964;179641963;179641962
N2AB	1576	4951;4952;4953	chr2:178777237;178777236;178777235	chr2:179641964;179641963;179641962
N2A	1576	4951;4952;4953	chr2:178777237;178777236;178777235	chr2:179641964;179641963;179641962
N2B	1530	4813;4814;4815	chr2:178777237;178777236;178777235	chr2:179641964;179641963;179641962
Novex-1	1530	4813;4814;4815	chr2:178777237;178777236;178777235	chr2:179641964;179641963;179641962
Novex-2	1530	4813;4814;4815	chr2:178777237;178777236;178777235	chr2:179641964;179641963;179641962
Novex-3	1576	4951;4952;4953	chr2:178777237;178777236;178777235	chr2:179641964;179641963;179641962

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-7
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.6123
• 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	rs1249517281	None	0.002	N	0.277	0.131	0.166414681773	gnomAD-4.0.0	1.20041E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3126E-06	0	0
K/T	rs201686366	-0.537	0.27	N	0.407	0.318	0.319402600006	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
K/T	rs201686366	-0.537	0.27	N	0.407	0.318	0.319402600006	gnomAD-4.0.0	1.59067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85691E-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
K/A	0.2298	likely_benign	0.1887	benign	-0.321	Destabilizing	0.001	N	0.303	neutral	None	None	None	None	N
K/C	0.6369	likely_pathogenic	0.5689	pathogenic	-0.455	Destabilizing	0.981	D	0.531	neutral	None	None	None	None	N
K/D	0.5454	ambiguous	0.4868	ambiguous	-0.06	Destabilizing	0.329	N	0.446	neutral	None	None	None	None	N
K/E	0.1788	likely_benign	0.1645	benign	0.022	Stabilizing	0.425	N	0.401	neutral	N	0.435788904	None	None	N
K/F	0.6433	likely_pathogenic	0.5768	pathogenic	-0.108	Destabilizing	0.944	D	0.548	neutral	None	None	None	None	N
K/G	0.3749	ambiguous	0.3168	benign	-0.639	Destabilizing	0.176	N	0.401	neutral	None	None	None	None	N
K/H	0.2562	likely_benign	0.2129	benign	-0.859	Destabilizing	0.944	D	0.519	neutral	None	None	None	None	N
K/I	0.2457	likely_benign	0.2229	benign	0.477	Stabilizing	0.642	D	0.547	neutral	N	0.513133156	None	None	N
K/L	0.2607	likely_benign	0.2207	benign	0.477	Stabilizing	0.495	N	0.463	neutral	None	None	None	None	N
K/M	0.1634	likely_benign	0.1457	benign	0.155	Stabilizing	0.981	D	0.514	neutral	None	None	None	None	N
K/N	0.2855	likely_benign	0.2436	benign	-0.285	Destabilizing	0.002	N	0.277	neutral	N	0.506128699	None	None	N
K/P	0.6724	likely_pathogenic	0.5742	pathogenic	0.241	Stabilizing	0.828	D	0.479	neutral	None	None	None	None	N
K/Q	0.1282	likely_benign	0.1125	benign	-0.346	Destabilizing	0.642	D	0.426	neutral	N	0.501550173	None	None	N
K/R	0.0783	likely_benign	0.0761	benign	-0.408	Destabilizing	0.006	N	0.251	neutral	N	0.494522144	None	None	N
K/S	0.3101	likely_benign	0.2604	benign	-0.834	Destabilizing	0.004	N	0.287	neutral	None	None	None	None	N
K/T	0.1182	likely_benign	0.1026	benign	-0.563	Destabilizing	0.27	N	0.407	neutral	N	0.482902856	None	None	N
K/V	0.234	likely_benign	0.2049	benign	0.241	Stabilizing	0.329	N	0.483	neutral	None	None	None	None	N
K/W	0.6522	likely_pathogenic	0.5966	pathogenic	-0.052	Destabilizing	0.995	D	0.563	neutral	None	None	None	None	N
K/Y	0.5414	ambiguous	0.4832	ambiguous	0.237	Stabilizing	0.981	D	0.561	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.