TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29366	88321;88322;88323	chr2:178557058;178557057;178557056	chr2:179421785;179421784;179421783
N2AB	27725	83398;83399;83400	chr2:178557058;178557057;178557056	chr2:179421785;179421784;179421783
N2A	26798	80617;80618;80619	chr2:178557058;178557057;178557056	chr2:179421785;179421784;179421783
N2B	20301	61126;61127;61128	chr2:178557058;178557057;178557056	chr2:179421785;179421784;179421783
Novex-1	20426	61501;61502;61503	chr2:178557058;178557057;178557056	chr2:179421785;179421784;179421783
Novex-2	20493	61702;61703;61704	chr2:178557058;178557057;178557056	chr2:179421785;179421784;179421783
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: Fn3-102
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.761
• Predicted PPI site: I

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	None	None	0.324	N	0.495	0.105	0.128392430309	gnomAD-4.0.0	1.3685E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99452E-07	0	1.65662E-05

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	0.4824	ambiguous	0.3113	benign	-0.053	Destabilizing	0.207	N	0.52	neutral	None	None	None	None	I
K/C	0.7579	likely_pathogenic	0.6265	pathogenic	-0.117	Destabilizing	0.981	D	0.509	neutral	None	None	None	None	I
K/D	0.7824	likely_pathogenic	0.6335	pathogenic	0.101	Stabilizing	0.388	N	0.519	neutral	None	None	None	None	I
K/E	0.3421	ambiguous	0.219	benign	0.105	Stabilizing	0.193	N	0.501	neutral	N	0.482698855	None	None	I
K/F	0.8787	likely_pathogenic	0.7568	pathogenic	-0.278	Destabilizing	0.818	D	0.499	neutral	None	None	None	None	I
K/G	0.6548	likely_pathogenic	0.4836	ambiguous	-0.258	Destabilizing	0.388	N	0.54	neutral	None	None	None	None	I
K/H	0.4306	ambiguous	0.3189	benign	-0.597	Destabilizing	0.818	D	0.507	neutral	None	None	None	None	I
K/I	0.5146	ambiguous	0.3185	benign	0.409	Stabilizing	0.818	D	0.52	neutral	None	None	None	None	I
K/L	0.4849	ambiguous	0.3232	benign	0.409	Stabilizing	0.388	N	0.549	neutral	None	None	None	None	I
K/M	0.3903	ambiguous	0.2461	benign	0.312	Stabilizing	0.975	D	0.503	neutral	N	0.45922406	None	None	I
K/N	0.6477	likely_pathogenic	0.4646	ambiguous	0.283	Stabilizing	0.324	N	0.495	neutral	N	0.494417358	None	None	I
K/P	0.5525	ambiguous	0.4146	ambiguous	0.283	Stabilizing	0.001	N	0.187	neutral	None	None	None	None	I
K/Q	0.1963	likely_benign	0.1411	benign	0.082	Stabilizing	0.324	N	0.527	neutral	N	0.451271115	None	None	I
K/R	0.0768	likely_benign	0.0716	benign	-0.017	Destabilizing	0.001	N	0.117	neutral	N	0.459304707	None	None	I
K/S	0.6229	likely_pathogenic	0.4329	ambiguous	-0.232	Destabilizing	0.388	N	0.499	neutral	None	None	None	None	I
K/T	0.3672	ambiguous	0.2197	benign	-0.077	Destabilizing	0.324	N	0.553	neutral	N	0.499785893	None	None	I
K/V	0.4249	ambiguous	0.2609	benign	0.283	Stabilizing	0.69	D	0.503	neutral	None	None	None	None	I
K/W	0.862	likely_pathogenic	0.7575	pathogenic	-0.271	Destabilizing	0.981	D	0.607	neutral	None	None	None	None	I
K/Y	0.7748	likely_pathogenic	0.6243	pathogenic	0.085	Stabilizing	0.818	D	0.526	neutral	None	None	None	None	I

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.