TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8408	25447;25448;25449	chr2:178717652;178717651;178717650	chr2:179582379;179582378;179582377
N2AB	8091	24496;24497;24498	chr2:178717652;178717651;178717650	chr2:179582379;179582378;179582377
N2A	7164	21715;21716;21717	chr2:178717652;178717651;178717650	chr2:179582379;179582378;179582377
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-69
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.4264
• 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
T/I	rs201432372	-0.168	0.001	N	0.261	0.071	None	gnomAD-2.1.1	3.08038E-04	None	None	None	None	I	None	3.35515E-03	1.41804E-04	None	0	0	None	0	None	0	0	0
T/I	rs201432372	-0.168	0.001	N	0.261	0.071	None	gnomAD-3.1.2	7.42971E-04	None	None	None	None	I	None	2.63145E-03	1.31044E-04	0	0	0	None	0	0	1.47E-05	0	4.78469E-04
T/I	rs201432372	-0.168	0.001	N	0.261	0.071	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
T/I	rs201432372	-0.168	0.001	N	0.261	0.071	None	gnomAD-4.0.0	1.35743E-04	None	None	None	None	I	None	2.62667E-03	1.16725E-04	None	0	0	None	0	0	5.93436E-06	0	1.28102E-04

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	0.1176	likely_benign	0.1152	benign	-1.135	Destabilizing	0.001	N	0.243	neutral	N	0.48394481	None	None	I
T/C	0.5162	ambiguous	0.5266	ambiguous	-0.605	Destabilizing	0.753	D	0.535	neutral	None	None	None	None	I
T/D	0.643	likely_pathogenic	0.7024	pathogenic	-0.561	Destabilizing	0.039	N	0.483	neutral	None	None	None	None	I
T/E	0.467	ambiguous	0.5396	ambiguous	-0.488	Destabilizing	0.119	N	0.47	neutral	None	None	None	None	I
T/F	0.3213	likely_benign	0.3674	ambiguous	-1.088	Destabilizing	0.335	N	0.607	neutral	None	None	None	None	I
T/G	0.3567	ambiguous	0.3911	ambiguous	-1.467	Destabilizing	0.065	N	0.417	neutral	None	None	None	None	I
T/H	0.3279	likely_benign	0.3941	ambiguous	-1.727	Destabilizing	0.803	D	0.547	neutral	None	None	None	None	I
T/I	0.2352	likely_benign	0.2106	benign	-0.309	Destabilizing	0.001	N	0.261	neutral	N	0.436527501	None	None	I
T/K	0.2687	likely_benign	0.3341	benign	-0.73	Destabilizing	0.029	N	0.415	neutral	N	0.494024122	None	None	I
T/L	0.1315	likely_benign	0.1378	benign	-0.309	Destabilizing	0.003	N	0.325	neutral	None	None	None	None	I
T/M	0.0914	likely_benign	0.0942	benign	-0.001	Destabilizing	0.001	N	0.271	neutral	None	None	None	None	I
T/N	0.2075	likely_benign	0.2473	benign	-0.911	Destabilizing	0.039	N	0.353	neutral	None	None	None	None	I
T/P	0.3759	ambiguous	0.3994	ambiguous	-0.552	Destabilizing	0.058	N	0.558	neutral	N	0.485972726	None	None	I
T/Q	0.2839	likely_benign	0.3292	benign	-0.927	Destabilizing	0.081	N	0.557	neutral	None	None	None	None	I
T/R	0.2207	likely_benign	0.2772	benign	-0.668	Destabilizing	0.001	N	0.333	neutral	N	0.489504672	None	None	I
T/S	0.1495	likely_benign	0.1683	benign	-1.208	Destabilizing	None	N	0.143	neutral	N	0.517570017	None	None	I
T/V	0.1881	likely_benign	0.2035	benign	-0.552	Destabilizing	0.001	N	0.129	neutral	None	None	None	None	I
T/W	0.6426	likely_pathogenic	0.6861	pathogenic	-1.056	Destabilizing	0.976	D	0.549	neutral	None	None	None	None	I
T/Y	0.3238	likely_benign	0.3606	ambiguous	-0.796	Destabilizing	0.782	D	0.615	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.