TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2657	8194;8195;8196	chr2:178771358;178771357;178771356	chr2:179636085;179636084;179636083
N2AB	2657	8194;8195;8196	chr2:178771358;178771357;178771356	chr2:179636085;179636084;179636083
N2A	2657	8194;8195;8196	chr2:178771358;178771357;178771356	chr2:179636085;179636084;179636083
N2B	2611	8056;8057;8058	chr2:178771358;178771357;178771356	chr2:179636085;179636084;179636083
Novex-1	2611	8056;8057;8058	chr2:178771358;178771357;178771356	chr2:179636085;179636084;179636083
Novex-2	2611	8056;8057;8058	chr2:178771358;178771357;178771356	chr2:179636085;179636084;179636083
Novex-3	2657	8194;8195;8196	chr2:178771358;178771357;178771356	chr2:179636085;179636084;179636083

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-16
• Domain position: 37
• Structural Position: 55
• Q(SASA): 0.4115
• 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	None	None	0.309	N	0.349	0.309	0.315903272564	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2664	likely_benign	0.2743	benign	0.03	Stabilizing	0.543	D	0.323	neutral	None	None	None	None	N
K/C	0.5525	ambiguous	0.566	pathogenic	-0.298	Destabilizing	0.996	D	0.435	neutral	None	None	None	None	N
K/D	0.3715	ambiguous	0.367	ambiguous	-0.005	Destabilizing	0.742	D	0.365	neutral	None	None	None	None	N
K/E	0.1071	likely_benign	0.1036	benign	0.009	Stabilizing	0.309	N	0.349	neutral	N	0.506871151	None	None	N
K/F	0.5516	ambiguous	0.5497	ambiguous	-0.15	Destabilizing	0.953	D	0.429	neutral	None	None	None	None	N
K/G	0.3792	ambiguous	0.3787	ambiguous	-0.17	Destabilizing	0.742	D	0.37	neutral	None	None	None	None	N
K/H	0.2206	likely_benign	0.2226	benign	-0.367	Destabilizing	0.02	N	0.234	neutral	None	None	None	None	N
K/I	0.1748	likely_benign	0.1678	benign	0.481	Stabilizing	0.939	D	0.435	neutral	N	0.516488019	None	None	N
K/L	0.2416	likely_benign	0.2354	benign	0.481	Stabilizing	0.742	D	0.375	neutral	None	None	None	None	N
K/M	0.1619	likely_benign	0.1536	benign	0.142	Stabilizing	0.984	D	0.369	neutral	None	None	None	None	N
K/N	0.1926	likely_benign	0.1968	benign	0.085	Stabilizing	0.684	D	0.282	neutral	N	0.509034581	None	None	N
K/P	0.8872	likely_pathogenic	0.8616	pathogenic	0.359	Stabilizing	0.984	D	0.355	neutral	None	None	None	None	N
K/Q	0.0891	likely_benign	0.0904	benign	-0.043	Destabilizing	0.078	N	0.163	neutral	N	0.454111617	None	None	N
K/R	0.0833	likely_benign	0.085	benign	-0.092	Destabilizing	0.007	N	0.205	neutral	N	0.502275922	None	None	N
K/S	0.2389	likely_benign	0.2563	benign	-0.36	Destabilizing	0.742	D	0.277	neutral	None	None	None	None	N
K/T	0.1328	likely_benign	0.1349	benign	-0.197	Destabilizing	0.684	D	0.373	neutral	N	0.515003864	None	None	N
K/V	0.1909	likely_benign	0.1828	benign	0.359	Stabilizing	0.854	D	0.397	neutral	None	None	None	None	N
K/W	0.6877	likely_pathogenic	0.6977	pathogenic	-0.2	Destabilizing	0.996	D	0.447	neutral	None	None	None	None	N
K/Y	0.4588	ambiguous	0.4532	ambiguous	0.152	Stabilizing	0.91	D	0.417	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.