TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18334	55225;55226;55227	chr2:178602402;178602401;178602400	chr2:179467129;179467128;179467127
N2AB	16693	50302;50303;50304	chr2:178602402;178602401;178602400	chr2:179467129;179467128;179467127
N2A	15766	47521;47522;47523	chr2:178602402;178602401;178602400	chr2:179467129;179467128;179467127
N2B	9269	28030;28031;28032	chr2:178602402;178602401;178602400	chr2:179467129;179467128;179467127
Novex-1	9394	28405;28406;28407	chr2:178602402;178602401;178602400	chr2:179467129;179467128;179467127
Novex-2	9461	28606;28607;28608	chr2:178602402;178602401;178602400	chr2:179467129;179467128;179467127
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-21
• Domain position: 63
• Structural Position: 91
• Q(SASA): 0.2049
• 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
C/R	rs1375579390	None	0.602	N	0.645	0.424	0.706878895572	gnomAD-4.0.0	8.21536E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19885E-06	0	6.6313E-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
C/A	0.3816	ambiguous	0.3393	benign	-1.46	Destabilizing	0.104	N	0.369	neutral	None	None	None	None	N
C/D	0.7974	likely_pathogenic	0.775	pathogenic	0.251	Stabilizing	0.667	D	0.656	neutral	None	None	None	None	N
C/E	0.8525	likely_pathogenic	0.8289	pathogenic	0.377	Stabilizing	0.667	D	0.655	neutral	None	None	None	None	N
C/F	0.1348	likely_benign	0.099	benign	-0.912	Destabilizing	None	N	0.492	neutral	N	0.425934	None	None	N
C/G	0.2423	likely_benign	0.2369	benign	-1.763	Destabilizing	0.301	N	0.621	neutral	N	0.513131697	None	None	N
C/H	0.5194	ambiguous	0.4732	ambiguous	-1.602	Destabilizing	0.497	N	0.644	neutral	None	None	None	None	N
C/I	0.4488	ambiguous	0.3299	benign	-0.683	Destabilizing	0.22	N	0.547	neutral	None	None	None	None	N
C/K	0.8375	likely_pathogenic	0.8295	pathogenic	-0.404	Destabilizing	0.497	N	0.654	neutral	None	None	None	None	N
C/L	0.402	ambiguous	0.293	benign	-0.683	Destabilizing	0.055	N	0.506	neutral	None	None	None	None	N
C/M	0.4946	ambiguous	0.4184	ambiguous	0.085	Stabilizing	0.859	D	0.591	neutral	None	None	None	None	N
C/N	0.5989	likely_pathogenic	0.5669	pathogenic	-0.612	Destabilizing	0.667	D	0.646	neutral	None	None	None	None	N
C/P	0.9889	likely_pathogenic	0.9845	pathogenic	-0.916	Destabilizing	0.859	D	0.639	neutral	None	None	None	None	N
C/Q	0.7171	likely_pathogenic	0.6894	pathogenic	-0.39	Destabilizing	0.667	D	0.637	neutral	None	None	None	None	N
C/R	0.5985	likely_pathogenic	0.5666	pathogenic	-0.412	Destabilizing	0.602	D	0.645	neutral	N	0.487902877	None	None	N
C/S	0.3802	ambiguous	0.3519	ambiguous	-1.162	Destabilizing	0.175	N	0.565	neutral	N	0.507032444	None	None	N
C/T	0.4553	ambiguous	0.4105	ambiguous	-0.836	Destabilizing	0.364	N	0.561	neutral	None	None	None	None	N
C/V	0.3743	ambiguous	0.2859	benign	-0.916	Destabilizing	0.104	N	0.501	neutral	None	None	None	None	N
C/W	0.4412	ambiguous	0.3545	ambiguous	-0.919	Destabilizing	0.602	D	0.599	neutral	N	0.520943104	None	None	N
C/Y	0.1693	likely_benign	0.1265	benign	-0.856	Destabilizing	None	N	0.481	neutral	N	0.423333625	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.