TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31946	96061;96062;96063	chr2:178544393;178544392;178544391	chr2:179409120;179409119;179409118
N2AB	30305	91138;91139;91140	chr2:178544393;178544392;178544391	chr2:179409120;179409119;179409118
N2A	29378	88357;88358;88359	chr2:178544393;178544392;178544391	chr2:179409120;179409119;179409118
N2B	22881	68866;68867;68868	chr2:178544393;178544392;178544391	chr2:179409120;179409119;179409118
Novex-1	23006	69241;69242;69243	chr2:178544393;178544392;178544391	chr2:179409120;179409119;179409118
Novex-2	23073	69442;69443;69444	chr2:178544393;178544392;178544391	chr2:179409120;179409119;179409118
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-121
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0615
• 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	rs1405729797	None	0.198	N	0.331	0.222	0.385578977469	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs1405729797	None	0.198	N	0.331	0.222	0.385578977469	gnomAD-4.0.0	6.5741E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	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
L/A	0.799	likely_pathogenic	0.8328	pathogenic	-3.214	Highly Destabilizing	0.983	D	0.683	prob.neutral	None	None	None	None	N
L/C	0.8456	likely_pathogenic	0.8616	pathogenic	-2.407	Highly Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9994	pathogenic	-3.702	Highly Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
L/E	0.9936	likely_pathogenic	0.9949	pathogenic	-3.43	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
L/F	0.7177	likely_pathogenic	0.7419	pathogenic	-2.007	Highly Destabilizing	0.998	D	0.616	neutral	None	None	None	None	N
L/G	0.9852	likely_pathogenic	0.9878	pathogenic	-3.696	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
L/H	0.9909	likely_pathogenic	0.9925	pathogenic	-3.125	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/I	0.0968	likely_benign	0.1003	benign	-1.72	Destabilizing	0.923	D	0.556	neutral	None	None	None	None	N
L/K	0.9923	likely_pathogenic	0.9935	pathogenic	-2.791	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
L/M	0.2725	likely_benign	0.3073	benign	-1.92	Destabilizing	0.997	D	0.621	neutral	N	0.502920277	None	None	N
L/N	0.9952	likely_pathogenic	0.9963	pathogenic	-3.488	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
L/P	0.9859	likely_pathogenic	0.9877	pathogenic	-2.218	Highly Destabilizing	0.999	D	0.887	deleterious	N	0.481086611	None	None	N
L/Q	0.9814	likely_pathogenic	0.9851	pathogenic	-3.18	Highly Destabilizing	0.999	D	0.877	deleterious	N	0.4926075	None	None	N
L/R	0.9845	likely_pathogenic	0.9865	pathogenic	-2.694	Highly Destabilizing	0.999	D	0.881	deleterious	N	0.4926075	None	None	N
L/S	0.9799	likely_pathogenic	0.9849	pathogenic	-3.882	Highly Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
L/T	0.8504	likely_pathogenic	0.8778	pathogenic	-3.48	Highly Destabilizing	0.983	D	0.687	prob.neutral	None	None	None	None	N
L/V	0.0867	likely_benign	0.0915	benign	-2.218	Highly Destabilizing	0.198	N	0.331	neutral	N	0.333535553	None	None	N
L/W	0.9721	likely_pathogenic	0.9724	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/Y	0.9796	likely_pathogenic	0.9817	pathogenic	-2.212	Highly Destabilizing	0.999	D	0.748	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.