TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15264	46015;46016;46017	chr2:178620820;178620819;178620818	chr2:179485547;179485546;179485545
N2AB	13623	41092;41093;41094	chr2:178620820;178620819;178620818	chr2:179485547;179485546;179485545
N2A	12696	38311;38312;38313	chr2:178620820;178620819;178620818	chr2:179485547;179485546;179485545
N2B	6199	18820;18821;18822	chr2:178620820;178620819;178620818	chr2:179485547;179485546;179485545
Novex-1	6324	19195;19196;19197	chr2:178620820;178620819;178620818	chr2:179485547;179485546;179485545
Novex-2	6391	19396;19397;19398	chr2:178620820;178620819;178620818	chr2:179485547;179485546;179485545
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-104
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0484
• 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	None	None	1.0	D	0.813	0.72	0.752632724806	gnomAD-4.0.0	4.79222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29921E-06	0	0
L/P	None	None	1.0	D	0.915	0.865	0.911412973807	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-05	0
L/V	None	None	0.999	D	0.623	0.662	0.726062263	gnomAD-4.0.0	6.84603E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15969E-05	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	0.9643	likely_pathogenic	0.9585	pathogenic	-2.4	Highly Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
L/C	0.9549	likely_pathogenic	0.935	pathogenic	-1.47	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.075	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/E	0.9981	likely_pathogenic	0.998	pathogenic	-2.774	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/F	0.7204	likely_pathogenic	0.6981	pathogenic	-1.519	Destabilizing	1.0	D	0.813	deleterious	D	0.666459122	None	None	N
L/G	0.994	likely_pathogenic	0.9929	pathogenic	-2.935	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/H	0.9941	likely_pathogenic	0.9932	pathogenic	-2.858	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.729659832	None	None	N
L/I	0.3914	ambiguous	0.405	ambiguous	-0.766	Destabilizing	0.999	D	0.617	neutral	D	0.687518662	None	None	N
L/K	0.9954	likely_pathogenic	0.9953	pathogenic	-1.885	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/M	0.3366	likely_benign	0.3482	ambiguous	-0.991	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
L/N	0.9981	likely_pathogenic	0.9979	pathogenic	-2.675	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/P	0.9989	likely_pathogenic	0.9989	pathogenic	-1.307	Destabilizing	1.0	D	0.915	deleterious	D	0.729659832	None	None	N
L/Q	0.9882	likely_pathogenic	0.9884	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
L/R	0.9906	likely_pathogenic	0.9896	pathogenic	-2.207	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.729659832	None	None	N
L/S	0.9953	likely_pathogenic	0.9947	pathogenic	-3.01	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/T	0.9872	likely_pathogenic	0.9861	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/V	0.4587	ambiguous	0.4479	ambiguous	-1.307	Destabilizing	0.999	D	0.623	neutral	D	0.689781353	None	None	N
L/W	0.9827	likely_pathogenic	0.9799	pathogenic	-1.788	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/Y	0.9846	likely_pathogenic	0.9808	pathogenic	-1.693	Destabilizing	1.0	D	0.869	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.