TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17029	51310;51311;51312	chr2:178611044;178611043;178611042	chr2:179475771;179475770;179475769
N2AB	15388	46387;46388;46389	chr2:178611044;178611043;178611042	chr2:179475771;179475770;179475769
N2A	14461	43606;43607;43608	chr2:178611044;178611043;178611042	chr2:179475771;179475770;179475769
N2B	7964	24115;24116;24117	chr2:178611044;178611043;178611042	chr2:179475771;179475770;179475769
Novex-1	8089	24490;24491;24492	chr2:178611044;178611043;178611042	chr2:179475771;179475770;179475769
Novex-2	8156	24691;24692;24693	chr2:178611044;178611043;178611042	chr2:179475771;179475770;179475769
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: Ig-111
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0729
• 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/R	None	None	0.761	D	0.842	0.568	0.766064486095	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
L/V	None	None	0.006	N	0.341	0.091	0.185906805712	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.5457	ambiguous	0.5937	pathogenic	-2.937	Highly Destabilizing	0.547	D	0.705	prob.neutral	None	None	None	None	N
L/C	0.7807	likely_pathogenic	0.8075	pathogenic	-2.76	Highly Destabilizing	0.985	D	0.8	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9991	pathogenic	-3.52	Highly Destabilizing	0.894	D	0.857	deleterious	None	None	None	None	N
L/E	0.9906	likely_pathogenic	0.9922	pathogenic	-3.268	Highly Destabilizing	0.809	D	0.839	deleterious	None	None	None	None	N
L/F	0.6819	likely_pathogenic	0.7533	pathogenic	-1.757	Destabilizing	0.894	D	0.77	deleterious	None	None	None	None	N
L/G	0.9443	likely_pathogenic	0.9537	pathogenic	-3.505	Highly Destabilizing	0.894	D	0.85	deleterious	None	None	None	None	N
L/H	0.985	likely_pathogenic	0.9891	pathogenic	-2.881	Highly Destabilizing	0.985	D	0.847	deleterious	None	None	None	None	N
L/I	0.1465	likely_benign	0.1764	benign	-1.265	Destabilizing	0.293	N	0.6	neutral	None	None	None	None	N
L/K	0.9907	likely_pathogenic	0.9918	pathogenic	-2.275	Highly Destabilizing	0.017	N	0.585	neutral	None	None	None	None	N
L/M	0.2073	likely_benign	0.2539	benign	-1.594	Destabilizing	0.864	D	0.74	deleterious	D	0.674465872	None	None	N
L/N	0.9904	likely_pathogenic	0.9936	pathogenic	-2.772	Highly Destabilizing	0.894	D	0.857	deleterious	None	None	None	None	N
L/P	0.9946	likely_pathogenic	0.9952	pathogenic	-1.808	Destabilizing	0.928	D	0.863	deleterious	D	0.675398045	None	None	N
L/Q	0.9629	likely_pathogenic	0.9699	pathogenic	-2.599	Highly Destabilizing	0.761	D	0.841	deleterious	D	0.675398045	None	None	N
L/R	0.9776	likely_pathogenic	0.9782	pathogenic	-2.008	Highly Destabilizing	0.761	D	0.842	deleterious	D	0.675398045	None	None	N
L/S	0.928	likely_pathogenic	0.9528	pathogenic	-3.479	Highly Destabilizing	0.809	D	0.813	deleterious	None	None	None	None	N
L/T	0.7469	likely_pathogenic	0.8091	pathogenic	-3.07	Highly Destabilizing	0.894	D	0.781	deleterious	None	None	None	None	N
L/V	0.1252	likely_benign	0.1444	benign	-1.808	Destabilizing	0.006	N	0.341	neutral	N	0.477947465	None	None	N
L/W	0.9695	likely_pathogenic	0.9747	pathogenic	-2.104	Highly Destabilizing	0.995	D	0.812	deleterious	None	None	None	None	N
L/Y	0.9737	likely_pathogenic	0.9812	pathogenic	-1.905	Destabilizing	0.945	D	0.812	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.