TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1739	5440;5441;5442	chr2:178776649;178776648;178776647	chr2:179641376;179641375;179641374
N2AB	1739	5440;5441;5442	chr2:178776649;178776648;178776647	chr2:179641376;179641375;179641374
N2A	1739	5440;5441;5442	chr2:178776649;178776648;178776647	chr2:179641376;179641375;179641374
N2B	1693	5302;5303;5304	chr2:178776649;178776648;178776647	chr2:179641376;179641375;179641374
Novex-1	1693	5302;5303;5304	chr2:178776649;178776648;178776647	chr2:179641376;179641375;179641374
Novex-2	1693	5302;5303;5304	chr2:178776649;178776648;178776647	chr2:179641376;179641375;179641374
Novex-3	1739	5440;5441;5442	chr2:178776649;178776648;178776647	chr2:179641376;179641375;179641374

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-8
• Domain position: 37
• Structural Position: 49
• Q(SASA): 0.2362
• 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
L/F	rs762699336	-1.537	1.0	N	0.657	0.371	0.637347744031	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.83E-06	0
L/F	rs762699336	-1.537	1.0	N	0.657	0.371	0.637347744031	gnomAD-4.0.0	3.18136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85652E-06	1.43271E-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
L/A	0.8261	likely_pathogenic	0.816	pathogenic	-2.513	Highly Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
L/C	0.8442	likely_pathogenic	0.8188	pathogenic	-1.903	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
L/D	0.9803	likely_pathogenic	0.9782	pathogenic	-2.857	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/E	0.8504	likely_pathogenic	0.8371	pathogenic	-2.688	Highly Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
L/F	0.2823	likely_benign	0.285	benign	-1.531	Destabilizing	1.0	D	0.657	neutral	N	0.463085242	None	None	N
L/G	0.9428	likely_pathogenic	0.9404	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
L/H	0.6283	likely_pathogenic	0.6215	pathogenic	-2.376	Highly Destabilizing	1.0	D	0.736	prob.delet.	D	0.642317686	None	None	N
L/I	0.2882	likely_benign	0.2784	benign	-1.154	Destabilizing	0.999	D	0.463	neutral	D	0.599489176	None	None	N
L/K	0.7775	likely_pathogenic	0.7654	pathogenic	-1.888	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
L/M	0.2106	likely_benign	0.2082	benign	-1.169	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
L/N	0.8315	likely_pathogenic	0.829	pathogenic	-2.108	Highly Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
L/P	0.9986	likely_pathogenic	0.9984	pathogenic	-1.587	Destabilizing	1.0	D	0.741	deleterious	D	0.731496222	None	None	N
L/Q	0.5002	ambiguous	0.4861	ambiguous	-2.073	Highly Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
L/R	0.6935	likely_pathogenic	0.669	pathogenic	-1.491	Destabilizing	1.0	D	0.742	deleterious	D	0.555482617	None	None	N
L/S	0.8146	likely_pathogenic	0.8188	pathogenic	-2.763	Highly Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
L/T	0.6815	likely_pathogenic	0.6882	pathogenic	-2.466	Highly Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/V	0.3274	likely_benign	0.3114	benign	-1.587	Destabilizing	0.999	D	0.515	neutral	D	0.587154863	None	None	N
L/W	0.5647	likely_pathogenic	0.5675	pathogenic	-1.869	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
L/Y	0.5874	likely_pathogenic	0.596	pathogenic	-1.619	Destabilizing	1.0	D	0.736	prob.delet.	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.