TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17401	52426;52427;52428	chr2:178608810;178608809;178608808	chr2:179473537;179473536;179473535
N2AB	15760	47503;47504;47505	chr2:178608810;178608809;178608808	chr2:179473537;179473536;179473535
N2A	14833	44722;44723;44724	chr2:178608810;178608809;178608808	chr2:179473537;179473536;179473535
N2B	8336	25231;25232;25233	chr2:178608810;178608809;178608808	chr2:179473537;179473536;179473535
Novex-1	8461	25606;25607;25608	chr2:178608810;178608809;178608808	chr2:179473537;179473536;179473535
Novex-2	8528	25807;25808;25809	chr2:178608810;178608809;178608808	chr2:179473537;179473536;179473535
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-14
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2076
• Predicted PPI site: I

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
I/T	rs1410389607	None	1.0	D	0.807	0.556	0.750041221393	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs1410389607	None	1.0	D	0.807	0.556	0.750041221393	gnomAD-4.0.0	6.58146E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47228E-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
I/A	0.9873	likely_pathogenic	0.9898	pathogenic	-2.488	Highly Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
I/C	0.9849	likely_pathogenic	0.9894	pathogenic	-1.545	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
I/D	0.9985	likely_pathogenic	0.9989	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
I/E	0.996	likely_pathogenic	0.997	pathogenic	-2.432	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
I/F	0.9559	likely_pathogenic	0.9692	pathogenic	-1.648	Destabilizing	1.0	D	0.823	deleterious	D	0.53358895	None	None	I
I/G	0.9969	likely_pathogenic	0.9976	pathogenic	-2.939	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
I/H	0.9977	likely_pathogenic	0.9985	pathogenic	-2.258	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
I/K	0.992	likely_pathogenic	0.9941	pathogenic	-1.872	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
I/L	0.61	likely_pathogenic	0.6265	pathogenic	-1.229	Destabilizing	0.993	D	0.383	neutral	N	0.482554641	None	None	I
I/M	0.6541	likely_pathogenic	0.6908	pathogenic	-0.906	Destabilizing	1.0	D	0.805	deleterious	D	0.536123845	None	None	I
I/N	0.9668	likely_pathogenic	0.975	pathogenic	-1.892	Destabilizing	1.0	D	0.847	deleterious	D	0.537137804	None	None	I
I/P	0.9836	likely_pathogenic	0.9882	pathogenic	-1.625	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
I/Q	0.9957	likely_pathogenic	0.9969	pathogenic	-1.951	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
I/R	0.9918	likely_pathogenic	0.994	pathogenic	-1.321	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
I/S	0.9889	likely_pathogenic	0.9915	pathogenic	-2.543	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.536377335	None	None	I
I/T	0.9709	likely_pathogenic	0.9757	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.807	deleterious	D	0.536377335	None	None	I
I/V	0.1565	likely_benign	0.1656	benign	-1.625	Destabilizing	0.993	D	0.374	neutral	N	0.500437333	None	None	I
I/W	0.9983	likely_pathogenic	0.999	pathogenic	-1.931	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
I/Y	0.9916	likely_pathogenic	0.9945	pathogenic	-1.704	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I

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.