TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29651	89176;89177;89178	chr2:178554160;178554159;178554158	chr2:179418887;179418886;179418885
N2AB	28010	84253;84254;84255	chr2:178554160;178554159;178554158	chr2:179418887;179418886;179418885
N2A	27083	81472;81473;81474	chr2:178554160;178554159;178554158	chr2:179418887;179418886;179418885
N2B	20586	61981;61982;61983	chr2:178554160;178554159;178554158	chr2:179418887;179418886;179418885
Novex-1	20711	62356;62357;62358	chr2:178554160;178554159;178554158	chr2:179418887;179418886;179418885
Novex-2	20778	62557;62558;62559	chr2:178554160;178554159;178554158	chr2:179418887;179418886;179418885
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-104
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.0977
• 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
T/N	None	None	1.0	N	0.677	0.39	0.478299402934	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
T/S	None	None	0.999	N	0.567	0.289	0.265929055128	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
T/A	0.2536	likely_benign	0.2764	benign	-0.929	Destabilizing	0.999	D	0.576	neutral	N	0.481714813	None	None	N
T/C	0.7273	likely_pathogenic	0.7355	pathogenic	-0.869	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
T/D	0.9048	likely_pathogenic	0.883	pathogenic	-1.365	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
T/E	0.8374	likely_pathogenic	0.8044	pathogenic	-1.251	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
T/F	0.6177	likely_pathogenic	0.6561	pathogenic	-0.647	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/G	0.7373	likely_pathogenic	0.7585	pathogenic	-1.294	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/H	0.7348	likely_pathogenic	0.7503	pathogenic	-1.581	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
T/I	0.2882	likely_benign	0.302	benign	-0.01	Destabilizing	1.0	D	0.749	deleterious	D	0.522850045	None	None	N
T/K	0.865	likely_pathogenic	0.8557	pathogenic	-0.97	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/L	0.2191	likely_benign	0.2339	benign	-0.01	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
T/M	0.1169	likely_benign	0.1341	benign	0.093	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/N	0.4357	ambiguous	0.452	ambiguous	-1.363	Destabilizing	1.0	D	0.677	prob.neutral	N	0.483120391	None	None	N
T/P	0.9061	likely_pathogenic	0.915	pathogenic	-0.283	Destabilizing	1.0	D	0.756	deleterious	N	0.516228256	None	None	N
T/Q	0.7292	likely_pathogenic	0.7306	pathogenic	-1.316	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/R	0.8236	likely_pathogenic	0.8199	pathogenic	-0.968	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/S	0.3726	ambiguous	0.4027	ambiguous	-1.516	Destabilizing	0.999	D	0.567	neutral	N	0.469153512	None	None	N
T/V	0.2056	likely_benign	0.2215	benign	-0.283	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
T/W	0.8586	likely_pathogenic	0.8596	pathogenic	-0.745	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
T/Y	0.6711	likely_pathogenic	0.6672	pathogenic	-0.432	Destabilizing	1.0	D	0.809	deleterious	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.