TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23529	70810;70811;70812	chr2:178575547;178575546;178575545	chr2:179440274;179440273;179440272
N2AB	21888	65887;65888;65889	chr2:178575547;178575546;178575545	chr2:179440274;179440273;179440272
N2A	20961	63106;63107;63108	chr2:178575547;178575546;178575545	chr2:179440274;179440273;179440272
N2B	14464	43615;43616;43617	chr2:178575547;178575546;178575545	chr2:179440274;179440273;179440272
Novex-1	14589	43990;43991;43992	chr2:178575547;178575546;178575545	chr2:179440274;179440273;179440272
Novex-2	14656	44191;44192;44193	chr2:178575547;178575546;178575545	chr2:179440274;179440273;179440272
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-58
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.0852
• 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	rs1709769243	None	0.977	N	0.359	0.196	0.320256813643	gnomAD-4.0.0	2.73701E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69866E-06	0	1.65662E-05

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	0.6684	likely_pathogenic	0.6646	pathogenic	-1.832	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
A/D	0.9887	likely_pathogenic	0.991	pathogenic	-2.512	Highly Destabilizing	1.0	D	0.813	deleterious	N	0.50952217	None	None	N
A/E	0.976	likely_pathogenic	0.9807	pathogenic	-2.424	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
A/F	0.8738	likely_pathogenic	0.8714	pathogenic	-1.089	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/G	0.5478	ambiguous	0.5762	pathogenic	-1.607	Destabilizing	0.996	D	0.593	neutral	N	0.476440758	None	None	N
A/H	0.9886	likely_pathogenic	0.9903	pathogenic	-1.617	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
A/I	0.2611	likely_benign	0.2568	benign	-0.415	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/K	0.9928	likely_pathogenic	0.9944	pathogenic	-1.402	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
A/L	0.4287	ambiguous	0.4138	ambiguous	-0.415	Destabilizing	0.999	D	0.653	prob.neutral	None	None	None	None	N
A/M	0.5231	ambiguous	0.5394	ambiguous	-0.763	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
A/N	0.9312	likely_pathogenic	0.9463	pathogenic	-1.569	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/P	0.6166	likely_pathogenic	0.6424	pathogenic	-0.659	Destabilizing	1.0	D	0.813	deleterious	N	0.501255691	None	None	N
A/Q	0.9661	likely_pathogenic	0.9719	pathogenic	-1.624	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/R	0.9815	likely_pathogenic	0.9845	pathogenic	-1.199	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
A/S	0.317	likely_benign	0.3496	ambiguous	-1.951	Destabilizing	0.999	D	0.647	neutral	N	0.482517145	None	None	N
A/T	0.3031	likely_benign	0.3613	ambiguous	-1.76	Destabilizing	1.0	D	0.667	prob.neutral	N	0.502815916	None	None	N
A/V	0.1265	likely_benign	0.1278	benign	-0.659	Destabilizing	0.977	D	0.359	neutral	N	0.459006424	None	None	N
A/W	0.9931	likely_pathogenic	0.9938	pathogenic	-1.546	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/Y	0.9656	likely_pathogenic	0.9671	pathogenic	-1.109	Destabilizing	1.0	D	0.795	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.