TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17473	52642;52643;52644	chr2:178608466;178608465;178608464	chr2:179473193;179473192;179473191
N2AB	15832	47719;47720;47721	chr2:178608466;178608465;178608464	chr2:179473193;179473192;179473191
N2A	14905	44938;44939;44940	chr2:178608466;178608465;178608464	chr2:179473193;179473192;179473191
N2B	8408	25447;25448;25449	chr2:178608466;178608465;178608464	chr2:179473193;179473192;179473191
Novex-1	8533	25822;25823;25824	chr2:178608466;178608465;178608464	chr2:179473193;179473192;179473191
Novex-2	8600	26023;26024;26025	chr2:178608466;178608465;178608464	chr2:179473193;179473192;179473191
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-15
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1612
• 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
A/V	rs1408028554	-0.736	0.989	N	0.717	0.32	0.400613892164	gnomAD-4.0.0	2.08187E-06	None	None	None	None	N	None	0	2.45242E-05	None	0	0	None	0	0	1.81357E-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
A/C	0.527	ambiguous	0.5359	ambiguous	-0.869	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/D	0.6892	likely_pathogenic	0.7067	pathogenic	-1.707	Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
A/E	0.3849	ambiguous	0.4054	ambiguous	-1.818	Destabilizing	0.993	D	0.819	deleterious	N	0.504457558	None	None	N
A/F	0.574	likely_pathogenic	0.5909	pathogenic	-1.347	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/G	0.2502	likely_benign	0.2538	benign	-1.04	Destabilizing	0.977	D	0.662	neutral	N	0.51281535	None	None	N
A/H	0.662	likely_pathogenic	0.6836	pathogenic	-1.11	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
A/I	0.5096	ambiguous	0.494	ambiguous	-0.647	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	N
A/K	0.6686	likely_pathogenic	0.6825	pathogenic	-1.144	Destabilizing	0.995	D	0.817	deleterious	None	None	None	None	N
A/L	0.4618	ambiguous	0.464	ambiguous	-0.647	Destabilizing	0.983	D	0.803	deleterious	None	None	None	None	N
A/M	0.444	ambiguous	0.4357	ambiguous	-0.352	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/N	0.5785	likely_pathogenic	0.5842	pathogenic	-0.824	Destabilizing	0.998	D	0.88	deleterious	None	None	None	None	N
A/P	0.1736	likely_benign	0.1546	benign	-0.692	Destabilizing	0.117	N	0.438	neutral	N	0.447314924	None	None	N
A/Q	0.4358	ambiguous	0.4497	ambiguous	-1.171	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
A/R	0.582	likely_pathogenic	0.6159	pathogenic	-0.61	Destabilizing	0.998	D	0.842	deleterious	None	None	None	None	N
A/S	0.1273	likely_benign	0.1331	benign	-1.0	Destabilizing	0.977	D	0.69	prob.neutral	N	0.509462248	None	None	N
A/T	0.2295	likely_benign	0.2202	benign	-1.05	Destabilizing	0.989	D	0.761	deleterious	N	0.486063815	None	None	N
A/V	0.302	likely_benign	0.2892	benign	-0.692	Destabilizing	0.989	D	0.717	prob.delet.	N	0.511849192	None	None	N
A/W	0.913	likely_pathogenic	0.9166	pathogenic	-1.543	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
A/Y	0.6765	likely_pathogenic	0.6912	pathogenic	-1.203	Destabilizing	1.0	D	0.878	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.