TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22354	67285;67286;67287	chr2:178580227;178580226;178580225	chr2:179444954;179444953;179444952
N2AB	20713	62362;62363;62364	chr2:178580227;178580226;178580225	chr2:179444954;179444953;179444952
N2A	19786	59581;59582;59583	chr2:178580227;178580226;178580225	chr2:179444954;179444953;179444952
N2B	13289	40090;40091;40092	chr2:178580227;178580226;178580225	chr2:179444954;179444953;179444952
Novex-1	13414	40465;40466;40467	chr2:178580227;178580226;178580225	chr2:179444954;179444953;179444952
Novex-2	13481	40666;40667;40668	chr2:178580227;178580226;178580225	chr2:179444954;179444953;179444952
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: Fn3-50
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3665
• 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/A	rs1159944072	-0.992	0.894	N	0.354	0.119	0.187945064343	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
T/A	rs1159944072	-0.992	0.894	N	0.354	0.119	0.187945064343	gnomAD-4.0.0	3.42532E-06	None	None	None	None	I	None	0	2.2484E-05	None	0	0	None	0	0	3.5996E-06	0	0
T/I	None	None	0.997	N	0.579	0.307	0.276482976112	gnomAD-4.0.0	1.20043E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31262E-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
T/A	0.1523	likely_benign	0.1719	benign	-0.792	Destabilizing	0.894	D	0.354	neutral	N	0.503594202	None	None	I
T/C	0.5726	likely_pathogenic	0.5731	pathogenic	-0.438	Destabilizing	1.0	D	0.574	neutral	None	None	None	None	I
T/D	0.8598	likely_pathogenic	0.8956	pathogenic	-0.2	Destabilizing	0.995	D	0.572	neutral	None	None	None	None	I
T/E	0.6876	likely_pathogenic	0.7505	pathogenic	-0.262	Destabilizing	0.995	D	0.565	neutral	None	None	None	None	I
T/F	0.6165	likely_pathogenic	0.6957	pathogenic	-1.227	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	I
T/G	0.5444	ambiguous	0.5683	pathogenic	-0.942	Destabilizing	0.982	D	0.541	neutral	None	None	None	None	I
T/H	0.5729	likely_pathogenic	0.6392	pathogenic	-1.315	Destabilizing	1.0	D	0.705	prob.delet.	None	None	None	None	I
T/I	0.3583	ambiguous	0.4316	ambiguous	-0.499	Destabilizing	0.997	D	0.579	neutral	N	0.451448925	None	None	I
T/K	0.3791	ambiguous	0.5104	ambiguous	-0.555	Destabilizing	0.995	D	0.564	neutral	None	None	None	None	I
T/L	0.2319	likely_benign	0.2834	benign	-0.499	Destabilizing	0.991	D	0.59	neutral	None	None	None	None	I
T/M	0.1762	likely_benign	0.19	benign	-0.009	Destabilizing	1.0	D	0.547	neutral	None	None	None	None	I
T/N	0.3256	likely_benign	0.3747	ambiguous	-0.362	Destabilizing	0.993	D	0.569	neutral	N	0.480442187	None	None	I
T/P	0.3025	likely_benign	0.4285	ambiguous	-0.569	Destabilizing	0.997	D	0.574	neutral	N	0.495684008	None	None	I
T/Q	0.4489	ambiguous	0.5152	ambiguous	-0.705	Destabilizing	0.997	D	0.531	neutral	None	None	None	None	I
T/R	0.3866	ambiguous	0.51	ambiguous	-0.221	Destabilizing	0.997	D	0.583	neutral	None	None	None	None	I
T/S	0.1702	likely_benign	0.1706	benign	-0.625	Destabilizing	0.615	D	0.135	neutral	N	0.466366752	None	None	I
T/V	0.2311	likely_benign	0.2781	benign	-0.569	Destabilizing	0.991	D	0.572	neutral	None	None	None	None	I
T/W	0.9274	likely_pathogenic	0.9415	pathogenic	-1.114	Destabilizing	1.0	D	0.691	prob.delet.	None	None	None	None	I
T/Y	0.6382	likely_pathogenic	0.7023	pathogenic	-0.875	Destabilizing	0.999	D	0.731	deleterious	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.