TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17592	52999;53000;53001	chr2:178608013;178608012;178608011	chr2:179472740;179472739;179472738
N2AB	15951	48076;48077;48078	chr2:178608013;178608012;178608011	chr2:179472740;179472739;179472738
N2A	15024	45295;45296;45297	chr2:178608013;178608012;178608011	chr2:179472740;179472739;179472738
N2B	8527	25804;25805;25806	chr2:178608013;178608012;178608011	chr2:179472740;179472739;179472738
Novex-1	8652	26179;26180;26181	chr2:178608013;178608012;178608011	chr2:179472740;179472739;179472738
Novex-2	8719	26380;26381;26382	chr2:178608013;178608012;178608011	chr2:179472740;179472739;179472738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-16
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5452
• 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
P/A	rs541127460	None	0.767	N	0.419	0.301	0.236890367714	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	2.88351E-04	0	None	0	0	0	0	0
P/A	rs541127460	None	0.767	N	0.419	0.301	0.236890367714	gnomAD-4.0.0	6.57912E-06	None	None	None	None	N	None	0	0	None	2.88351E-04	0	None	0	0	0	0	0
P/H	None	None	1.0	N	0.821	0.483	0.691146523942	gnomAD-4.0.0	6.84579E-07	None	None	None	None	N	None	0	0	None	0	2.53331E-05	None	0	0	0	0	0
P/L	rs1559744241	None	0.999	N	0.795	0.442	0.807022764505	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
P/L	rs1559744241	None	0.999	N	0.795	0.442	0.807022764505	gnomAD-4.0.0	1.36916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79954E-06	0	0
P/S	None	None	0.998	N	0.768	0.377	0.366848117066	gnomAD-4.0.0	6.84586E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65821E-05
P/T	rs541127460	-1.59	0.999	N	0.782	0.39	0.531581166724	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	0	None	0	5.65E-05	None	1.63431E-04	None	0	0	0
P/T	rs541127460	-1.59	0.999	N	0.782	0.39	0.531581166724	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
P/T	rs541127460	-1.59	0.999	N	0.782	0.39	0.531581166724	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
P/T	rs541127460	-1.59	0.999	N	0.782	0.39	0.531581166724	gnomAD-4.0.0	1.17804E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.97663E-04	1.60205E-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
P/A	0.0896	likely_benign	0.0835	benign	-1.9	Destabilizing	0.767	D	0.419	neutral	N	0.511230329	None	None	N
P/C	0.6627	likely_pathogenic	0.5843	pathogenic	-1.348	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/D	0.6456	likely_pathogenic	0.6081	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/E	0.3534	ambiguous	0.3333	benign	-2.066	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/F	0.6616	likely_pathogenic	0.5819	pathogenic	-1.257	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/G	0.5422	ambiguous	0.5026	ambiguous	-2.31	Highly Destabilizing	0.997	D	0.749	deleterious	None	None	None	None	N
P/H	0.3815	ambiguous	0.346	ambiguous	-1.744	Destabilizing	1.0	D	0.821	deleterious	N	0.509270178	None	None	N
P/I	0.3248	likely_benign	0.2896	benign	-0.806	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/K	0.3978	ambiguous	0.3785	ambiguous	-1.773	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/L	0.1496	likely_benign	0.135	benign	-0.806	Destabilizing	0.999	D	0.795	deleterious	N	0.520119504	None	None	N
P/M	0.3277	likely_benign	0.2956	benign	-0.728	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/N	0.5696	likely_pathogenic	0.5207	ambiguous	-1.815	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
P/Q	0.2376	likely_benign	0.2238	benign	-1.837	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/R	0.3399	likely_benign	0.3085	benign	-1.333	Destabilizing	0.999	D	0.831	deleterious	D	0.526413213	None	None	N
P/S	0.2211	likely_benign	0.1988	benign	-2.339	Highly Destabilizing	0.998	D	0.768	deleterious	N	0.491468638	None	None	N
P/T	0.1717	likely_benign	0.1537	benign	-2.092	Highly Destabilizing	0.999	D	0.782	deleterious	N	0.489088781	None	None	N
P/V	0.2204	likely_benign	0.2004	benign	-1.142	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
P/W	0.8492	likely_pathogenic	0.8037	pathogenic	-1.552	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/Y	0.6305	likely_pathogenic	0.5687	pathogenic	-1.237	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.