TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21539	64840;64841;64842	chr2:178585129;178585128;178585127	chr2:179449856;179449855;179449854
N2AB	19898	59917;59918;59919	chr2:178585129;178585128;178585127	chr2:179449856;179449855;179449854
N2A	18971	57136;57137;57138	chr2:178585129;178585128;178585127	chr2:179449856;179449855;179449854
N2B	12474	37645;37646;37647	chr2:178585129;178585128;178585127	chr2:179449856;179449855;179449854
Novex-1	12599	38020;38021;38022	chr2:178585129;178585128;178585127	chr2:179449856;179449855;179449854
Novex-2	12666	38221;38222;38223	chr2:178585129;178585128;178585127	chr2:179449856;179449855;179449854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-124
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.1153
• 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	rs1060500431	None	1.0	N	0.843	0.399	0.557597400255	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs1060500431	None	1.0	N	0.843	0.399	0.557597400255	gnomAD-4.0.0	2.56433E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.79069E-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	0.9148	likely_pathogenic	0.8932	pathogenic	-2.689	Highly Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
L/C	0.8508	likely_pathogenic	0.833	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9994	pathogenic	-3.22	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/E	0.9957	likely_pathogenic	0.9947	pathogenic	-3.002	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/F	0.6394	likely_pathogenic	0.62	pathogenic	-1.57	Destabilizing	1.0	D	0.843	deleterious	N	0.512832548	None	None	N
L/G	0.9913	likely_pathogenic	0.9881	pathogenic	-3.214	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/H	0.99	likely_pathogenic	0.988	pathogenic	-2.608	Highly Destabilizing	1.0	D	0.881	deleterious	N	0.484053492	None	None	N
L/I	0.1056	likely_benign	0.102	benign	-1.16	Destabilizing	0.999	D	0.682	prob.neutral	N	0.432696896	None	None	N
L/K	0.9921	likely_pathogenic	0.9914	pathogenic	-1.941	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/M	0.2629	likely_benign	0.2518	benign	-1.296	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/N	0.9957	likely_pathogenic	0.9944	pathogenic	-2.329	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/P	0.9963	likely_pathogenic	0.9962	pathogenic	-1.654	Destabilizing	1.0	D	0.904	deleterious	N	0.484053492	None	None	N
L/Q	0.9799	likely_pathogenic	0.976	pathogenic	-2.208	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/R	0.9852	likely_pathogenic	0.984	pathogenic	-1.654	Destabilizing	1.0	D	0.9	deleterious	N	0.484053492	None	None	N
L/S	0.9909	likely_pathogenic	0.988	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/T	0.9557	likely_pathogenic	0.9418	pathogenic	-2.635	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/V	0.1267	likely_benign	0.121	benign	-1.654	Destabilizing	0.999	D	0.707	prob.neutral	N	0.460286142	None	None	N
L/W	0.9716	likely_pathogenic	0.9703	pathogenic	-1.952	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
L/Y	0.966	likely_pathogenic	0.9629	pathogenic	-1.724	Destabilizing	1.0	D	0.877	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.