TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31951	96076;96077;96078	chr2:178544378;178544377;178544376	chr2:179409105;179409104;179409103
N2AB	30310	91153;91154;91155	chr2:178544378;178544377;178544376	chr2:179409105;179409104;179409103
N2A	29383	88372;88373;88374	chr2:178544378;178544377;178544376	chr2:179409105;179409104;179409103
N2B	22886	68881;68882;68883	chr2:178544378;178544377;178544376	chr2:179409105;179409104;179409103
Novex-1	23011	69256;69257;69258	chr2:178544378;178544377;178544376	chr2:179409105;179409104;179409103
Novex-2	23078	69457;69458;69459	chr2:178544378;178544377;178544376	chr2:179409105;179409104;179409103
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: Fn3-121
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.4468
• 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/R	None	None	0.042	N	0.227	0.146	0.212008924253	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-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	0.1704	likely_benign	0.1725	benign	-0.338	Destabilizing	0.055	N	0.403	neutral	None	None	None	None	N
K/C	0.5022	ambiguous	0.5289	ambiguous	-0.344	Destabilizing	0.958	D	0.539	neutral	None	None	None	None	N
K/D	0.3355	likely_benign	0.3219	benign	-0.235	Destabilizing	None	N	0.189	neutral	None	None	None	None	N
K/E	0.1069	likely_benign	0.1011	benign	-0.165	Destabilizing	None	N	0.127	neutral	N	0.450467085	None	None	N
K/F	0.6244	likely_pathogenic	0.6431	pathogenic	-0.129	Destabilizing	0.859	D	0.554	neutral	None	None	None	None	N
K/G	0.245	likely_benign	0.2424	benign	-0.672	Destabilizing	0.104	N	0.475	neutral	None	None	None	None	N
K/H	0.2769	likely_benign	0.2865	benign	-1.108	Destabilizing	0.497	N	0.457	neutral	None	None	None	None	N
K/I	0.2141	likely_benign	0.2191	benign	0.508	Stabilizing	0.667	D	0.563	neutral	None	None	None	None	N
K/L	0.2503	likely_benign	0.2521	benign	0.508	Stabilizing	0.22	N	0.507	neutral	None	None	None	None	N
K/M	0.1519	likely_benign	0.1504	benign	0.411	Stabilizing	0.602	D	0.46	neutral	N	0.492159292	None	None	N
K/N	0.227	likely_benign	0.22	benign	-0.306	Destabilizing	0.096	N	0.19	neutral	D	0.524831558	None	None	N
K/P	0.4475	ambiguous	0.4401	ambiguous	0.257	Stabilizing	0.364	N	0.433	neutral	None	None	None	None	N
K/Q	0.1086	likely_benign	0.1091	benign	-0.431	Destabilizing	0.001	N	0.107	neutral	N	0.520020384	None	None	N
K/R	0.0904	likely_benign	0.0889	benign	-0.621	Destabilizing	0.042	N	0.227	neutral	N	0.516134717	None	None	N
K/S	0.2418	likely_benign	0.2411	benign	-0.849	Destabilizing	0.055	N	0.248	neutral	None	None	None	None	N
K/T	0.1205	likely_benign	0.1205	benign	-0.595	Destabilizing	0.175	N	0.363	neutral	N	0.494007219	None	None	N
K/V	0.2041	likely_benign	0.2081	benign	0.257	Stabilizing	0.22	N	0.498	neutral	None	None	None	None	N
K/W	0.6748	likely_pathogenic	0.6827	pathogenic	-0.05	Destabilizing	0.958	D	0.555	neutral	None	None	None	None	N
K/Y	0.4916	ambiguous	0.4931	ambiguous	0.238	Stabilizing	0.667	D	0.551	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.