TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16758	50497;50498;50499	chr2:178612139;178612138;178612137	chr2:179476866;179476865;179476864
N2AB	15117	45574;45575;45576	chr2:178612139;178612138;178612137	chr2:179476866;179476865;179476864
N2A	14190	42793;42794;42795	chr2:178612139;178612138;178612137	chr2:179476866;179476865;179476864
N2B	7693	23302;23303;23304	chr2:178612139;178612138;178612137	chr2:179476866;179476865;179476864
Novex-1	7818	23677;23678;23679	chr2:178612139;178612138;178612137	chr2:179476866;179476865;179476864
Novex-2	7885	23878;23879;23880	chr2:178612139;178612138;178612137	chr2:179476866;179476865;179476864
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-10
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2374
• 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/P	None	None	1.0	N	0.877	0.617	0.839773394438	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.9333	likely_pathogenic	0.919	pathogenic	-2.35	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
L/C	0.955	likely_pathogenic	0.9458	pathogenic	-1.778	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9987	pathogenic	-2.479	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/E	0.9941	likely_pathogenic	0.9935	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/F	0.8954	likely_pathogenic	0.8442	pathogenic	-1.528	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/G	0.9927	likely_pathogenic	0.9911	pathogenic	-2.822	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/H	0.9915	likely_pathogenic	0.9889	pathogenic	-2.242	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/I	0.335	likely_benign	0.3186	benign	-1.031	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
L/K	0.9892	likely_pathogenic	0.9873	pathogenic	-1.721	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/M	0.4997	ambiguous	0.4726	ambiguous	-0.988	Destabilizing	1.0	D	0.788	deleterious	D	0.599224133	None	None	N
L/N	0.993	likely_pathogenic	0.9913	pathogenic	-1.829	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/P	0.9379	likely_pathogenic	0.8731	pathogenic	-1.447	Destabilizing	1.0	D	0.877	deleterious	N	0.491471759	None	None	N
L/Q	0.9815	likely_pathogenic	0.9806	pathogenic	-1.844	Destabilizing	1.0	D	0.881	deleterious	D	0.692943007	None	None	N
L/R	0.9807	likely_pathogenic	0.9774	pathogenic	-1.324	Destabilizing	1.0	D	0.881	deleterious	D	0.692943007	None	None	N
L/S	0.9904	likely_pathogenic	0.989	pathogenic	-2.506	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/T	0.9209	likely_pathogenic	0.9223	pathogenic	-2.237	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/V	0.3007	likely_benign	0.2944	benign	-1.447	Destabilizing	0.999	D	0.705	prob.neutral	N	0.473712219	None	None	N
L/W	0.9899	likely_pathogenic	0.9861	pathogenic	-1.813	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
L/Y	0.9934	likely_pathogenic	0.9901	pathogenic	-1.543	Destabilizing	1.0	D	0.837	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.