TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24561	73906;73907;73908	chr2:178572451;178572450;178572449	chr2:179437178;179437177;179437176
N2AB	22920	68983;68984;68985	chr2:178572451;178572450;178572449	chr2:179437178;179437177;179437176
N2A	21993	66202;66203;66204	chr2:178572451;178572450;178572449	chr2:179437178;179437177;179437176
N2B	15496	46711;46712;46713	chr2:178572451;178572450;178572449	chr2:179437178;179437177;179437176
Novex-1	15621	47086;47087;47088	chr2:178572451;178572450;178572449	chr2:179437178;179437177;179437176
Novex-2	15688	47287;47288;47289	chr2:178572451;178572450;178572449	chr2:179437178;179437177;179437176
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-66
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.1905
• 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
S/L	None	None	0.911	N	0.617	0.361	0.445410361449	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.0689	likely_benign	0.0629	benign	-0.812	Destabilizing	0.001	N	0.206	neutral	N	0.411967412	None	None	N
S/C	0.2305	likely_benign	0.2011	benign	-0.464	Destabilizing	0.99	D	0.603	neutral	None	None	None	None	N
S/D	0.8857	likely_pathogenic	0.8614	pathogenic	0.483	Stabilizing	0.881	D	0.511	neutral	None	None	None	None	N
S/E	0.8952	likely_pathogenic	0.8848	pathogenic	0.465	Stabilizing	0.836	D	0.514	neutral	None	None	None	None	N
S/F	0.6073	likely_pathogenic	0.4969	ambiguous	-1.008	Destabilizing	0.99	D	0.683	prob.neutral	None	None	None	None	N
S/G	0.1589	likely_benign	0.1342	benign	-1.031	Destabilizing	0.772	D	0.502	neutral	None	None	None	None	N
S/H	0.8245	likely_pathogenic	0.7867	pathogenic	-1.312	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
S/I	0.4065	ambiguous	0.3334	benign	-0.338	Destabilizing	0.979	D	0.678	prob.neutral	None	None	None	None	N
S/K	0.965	likely_pathogenic	0.9571	pathogenic	-0.417	Destabilizing	0.932	D	0.522	neutral	None	None	None	None	N
S/L	0.2148	likely_benign	0.1689	benign	-0.338	Destabilizing	0.911	D	0.617	neutral	N	0.491236272	None	None	N
S/M	0.2961	likely_benign	0.2554	benign	-0.14	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
S/N	0.4048	ambiguous	0.3548	ambiguous	-0.267	Destabilizing	0.752	D	0.539	neutral	None	None	None	None	N
S/P	0.7425	likely_pathogenic	0.6252	pathogenic	-0.464	Destabilizing	0.009	N	0.317	neutral	N	0.493988576	None	None	N
S/Q	0.8395	likely_pathogenic	0.8153	pathogenic	-0.433	Destabilizing	0.99	D	0.545	neutral	None	None	None	None	N
S/R	0.9608	likely_pathogenic	0.9485	pathogenic	-0.294	Destabilizing	0.99	D	0.579	neutral	None	None	None	None	N
S/T	0.124	likely_benign	0.1064	benign	-0.447	Destabilizing	0.243	N	0.541	neutral	N	0.445733269	None	None	N
S/V	0.3214	likely_benign	0.2663	benign	-0.464	Destabilizing	0.718	D	0.616	neutral	None	None	None	None	N
S/W	0.8278	likely_pathogenic	0.7486	pathogenic	-0.9	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
S/Y	0.6037	likely_pathogenic	0.5126	ambiguous	-0.662	Destabilizing	0.997	D	0.683	prob.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.