TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29847	89764;89765;89766	chr2:178553361;178553360;178553359	chr2:179418088;179418087;179418086
N2AB	28206	84841;84842;84843	chr2:178553361;178553360;178553359	chr2:179418088;179418087;179418086
N2A	27279	82060;82061;82062	chr2:178553361;178553360;178553359	chr2:179418088;179418087;179418086
N2B	20782	62569;62570;62571	chr2:178553361;178553360;178553359	chr2:179418088;179418087;179418086
Novex-1	20907	62944;62945;62946	chr2:178553361;178553360;178553359	chr2:179418088;179418087;179418086
Novex-2	20974	63145;63146;63147	chr2:178553361;178553360;178553359	chr2:179418088;179418087;179418086
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: Ig-147
• Domain position: 6
• Structural Position: 9
• Q(SASA): 0.6918
• 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/I	rs760372724	-0.07	0.638	N	0.521	0.334	0.42264334713	gnomAD-2.1.1	8.3E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.65E-05	None	0	0	0
T/I	rs760372724	-0.07	0.638	N	0.521	0.334	0.42264334713	gnomAD-4.0.0	1.38176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.33019E-05	0
T/N	None	None	0.468	N	0.47	0.241	0.307966526162	gnomAD-4.0.0	6.90878E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0362E-07	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	0.146	likely_benign	0.141	benign	-0.367	Destabilizing	0.094	N	0.544	neutral	N	0.474544384	None	None	N
T/C	0.6685	likely_pathogenic	0.6207	pathogenic	-0.2	Destabilizing	0.947	D	0.531	neutral	None	None	None	None	N
T/D	0.5457	ambiguous	0.5218	ambiguous	0.423	Stabilizing	0.25	N	0.487	neutral	None	None	None	None	N
T/E	0.4546	ambiguous	0.4557	ambiguous	0.342	Stabilizing	0.25	N	0.514	neutral	None	None	None	None	N
T/F	0.5805	likely_pathogenic	0.5309	ambiguous	-0.946	Destabilizing	0.826	D	0.574	neutral	None	None	None	None	N
T/G	0.2936	likely_benign	0.2924	benign	-0.472	Destabilizing	0.25	N	0.503	neutral	None	None	None	None	N
T/H	0.3967	ambiguous	0.3906	ambiguous	-0.855	Destabilizing	0.947	D	0.569	neutral	None	None	None	None	N
T/I	0.4784	ambiguous	0.4462	ambiguous	-0.212	Destabilizing	0.638	D	0.521	neutral	N	0.516855154	None	None	N
T/K	0.285	likely_benign	0.3031	benign	-0.203	Destabilizing	0.25	N	0.503	neutral	None	None	None	None	N
T/L	0.2297	likely_benign	0.2234	benign	-0.212	Destabilizing	0.399	N	0.507	neutral	None	None	None	None	N
T/M	0.1836	likely_benign	0.179	benign	0.022	Stabilizing	0.982	D	0.521	neutral	None	None	None	None	N
T/N	0.17	likely_benign	0.1721	benign	0.007	Stabilizing	0.468	N	0.47	neutral	N	0.471581437	None	None	N
T/P	0.301	likely_benign	0.2623	benign	-0.236	Destabilizing	0.638	D	0.52	neutral	N	0.468293203	None	None	N
T/Q	0.306	likely_benign	0.3243	benign	-0.212	Destabilizing	0.057	N	0.337	neutral	None	None	None	None	N
T/R	0.3099	likely_benign	0.3157	benign	-0.028	Destabilizing	0.7	D	0.519	neutral	None	None	None	None	N
T/S	0.1562	likely_benign	0.1574	benign	-0.23	Destabilizing	0.002	N	0.334	neutral	N	0.42875338	None	None	N
T/V	0.3312	likely_benign	0.3065	benign	-0.236	Destabilizing	0.399	N	0.492	neutral	None	None	None	None	N
T/W	0.829	likely_pathogenic	0.7905	pathogenic	-0.952	Destabilizing	0.982	D	0.612	neutral	None	None	None	None	N
T/Y	0.497	ambiguous	0.4469	ambiguous	-0.652	Destabilizing	0.826	D	0.573	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.