TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21737	65434;65435;65436	chr2:178584342;178584341;178584340	chr2:179449069;179449068;179449067
N2AB	20096	60511;60512;60513	chr2:178584342;178584341;178584340	chr2:179449069;179449068;179449067
N2A	19169	57730;57731;57732	chr2:178584342;178584341;178584340	chr2:179449069;179449068;179449067
N2B	12672	38239;38240;38241	chr2:178584342;178584341;178584340	chr2:179449069;179449068;179449067
Novex-1	12797	38614;38615;38616	chr2:178584342;178584341;178584340	chr2:179449069;179449068;179449067
Novex-2	12864	38815;38816;38817	chr2:178584342;178584341;178584340	chr2:179449069;179449068;179449067
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-45
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2081
• 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/V	rs2048461875	None	0.619	N	0.335	0.126	0.224531998449	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.3501	ambiguous	0.2902	benign	-2.204	Highly Destabilizing	0.994	D	0.569	neutral	None	None	None	None	N
L/C	0.3965	ambiguous	0.3634	ambiguous	-1.633	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/D	0.8908	likely_pathogenic	0.8485	pathogenic	-1.704	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/E	0.4186	ambiguous	0.3675	ambiguous	-1.56	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/F	0.1558	likely_benign	0.1405	benign	-1.354	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
L/G	0.8095	likely_pathogenic	0.7475	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/H	0.2679	likely_benign	0.2268	benign	-1.888	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/I	0.0667	likely_benign	0.0655	benign	-0.929	Destabilizing	0.984	D	0.453	neutral	N	0.390285418	None	None	N
L/K	0.3188	likely_benign	0.2785	benign	-1.41	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/M	0.0854	likely_benign	0.0838	benign	-0.953	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
L/N	0.5967	likely_pathogenic	0.5006	ambiguous	-1.497	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/P	0.9853	likely_pathogenic	0.9827	pathogenic	-1.329	Destabilizing	1.0	D	0.883	deleterious	D	0.523466121	None	None	N
L/Q	0.1301	likely_benign	0.1221	benign	-1.492	Destabilizing	1.0	D	0.868	deleterious	N	0.453123388	None	None	N
L/R	0.2609	likely_benign	0.2245	benign	-1.052	Destabilizing	1.0	D	0.871	deleterious	N	0.459259927	None	None	N
L/S	0.4041	ambiguous	0.3295	benign	-2.3	Highly Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
L/T	0.2307	likely_benign	0.1941	benign	-2.02	Highly Destabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	N
L/V	0.0603	likely_benign	0.0605	benign	-1.329	Destabilizing	0.619	D	0.335	neutral	N	0.331154183	None	None	N
L/W	0.3114	likely_benign	0.2787	benign	-1.53	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/Y	0.3724	ambiguous	0.3273	benign	-1.272	Destabilizing	1.0	D	0.847	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.