TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29066	87421;87422;87423	chr2:178558158;178558157;178558156	chr2:179422885;179422884;179422883
N2AB	27425	82498;82499;82500	chr2:178558158;178558157;178558156	chr2:179422885;179422884;179422883
N2A	26498	79717;79718;79719	chr2:178558158;178558157;178558156	chr2:179422885;179422884;179422883
N2B	20001	60226;60227;60228	chr2:178558158;178558157;178558156	chr2:179422885;179422884;179422883
Novex-1	20126	60601;60602;60603	chr2:178558158;178558157;178558156	chr2:179422885;179422884;179422883
Novex-2	20193	60802;60803;60804	chr2:178558158;178558157;178558156	chr2:179422885;179422884;179422883
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-145
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0986
• 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
I/V	rs1702228996	None	0.993	N	0.463	0.286	0.384086055536	gnomAD-4.0.0	1.59132E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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
I/A	0.9303	likely_pathogenic	0.9305	pathogenic	-2.663	Highly Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
I/C	0.9213	likely_pathogenic	0.9261	pathogenic	-2.072	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
I/D	0.997	likely_pathogenic	0.9974	pathogenic	-2.863	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/E	0.9947	likely_pathogenic	0.9955	pathogenic	-2.607	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/F	0.2981	likely_benign	0.3025	benign	-1.66	Destabilizing	1.0	D	0.819	deleterious	N	0.458743534	None	None	N
I/G	0.989	likely_pathogenic	0.9893	pathogenic	-3.247	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
I/H	0.9779	likely_pathogenic	0.9818	pathogenic	-2.682	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
I/K	0.9831	likely_pathogenic	0.9869	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/L	0.1711	likely_benign	0.183	benign	-0.964	Destabilizing	0.993	D	0.523	neutral	N	0.501460761	None	None	N
I/M	0.2467	likely_benign	0.2576	benign	-0.917	Destabilizing	1.0	D	0.78	deleterious	N	0.470517913	None	None	N
I/N	0.9563	likely_pathogenic	0.9641	pathogenic	-2.594	Highly Destabilizing	1.0	D	0.88	deleterious	N	0.470771403	None	None	N
I/P	0.9952	likely_pathogenic	0.995	pathogenic	-1.513	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/Q	0.9857	likely_pathogenic	0.9883	pathogenic	-2.392	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
I/R	0.9752	likely_pathogenic	0.9802	pathogenic	-1.963	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
I/S	0.9453	likely_pathogenic	0.9517	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.853	deleterious	N	0.470264423	None	None	N
I/T	0.9211	likely_pathogenic	0.9312	pathogenic	-2.911	Highly Destabilizing	1.0	D	0.758	deleterious	N	0.469757444	None	None	N
I/V	0.1361	likely_benign	0.1311	benign	-1.513	Destabilizing	0.993	D	0.463	neutral	N	0.436465133	None	None	N
I/W	0.9676	likely_pathogenic	0.9728	pathogenic	-2.013	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
I/Y	0.8843	likely_pathogenic	0.9002	pathogenic	-1.737	Destabilizing	1.0	D	0.786	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.