TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30065	90418;90419;90420	chr2:178552707;178552706;178552705	chr2:179417434;179417433;179417432
N2AB	28424	85495;85496;85497	chr2:178552707;178552706;178552705	chr2:179417434;179417433;179417432
N2A	27497	82714;82715;82716	chr2:178552707;178552706;178552705	chr2:179417434;179417433;179417432
N2B	21000	63223;63224;63225	chr2:178552707;178552706;178552705	chr2:179417434;179417433;179417432
Novex-1	21125	63598;63599;63600	chr2:178552707;178552706;178552705	chr2:179417434;179417433;179417432
Novex-2	21192	63799;63800;63801	chr2:178552707;178552706;178552705	chr2:179417434;179417433;179417432
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-107
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1097
• 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
Y/C	None	None	1.0	D	0.869	0.696	0.79213374795	gnomAD-4.0.0	1.59104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85785E-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
Y/A	0.9954	likely_pathogenic	0.9909	pathogenic	-3.241	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/C	0.9696	likely_pathogenic	0.9249	pathogenic	-1.928	Destabilizing	1.0	D	0.869	deleterious	D	0.646065566	None	None	N
Y/D	0.9959	likely_pathogenic	0.9923	pathogenic	-3.73	Highly Destabilizing	1.0	D	0.912	deleterious	D	0.646469175	None	None	N
Y/E	0.9989	likely_pathogenic	0.9979	pathogenic	-3.511	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
Y/F	0.3647	ambiguous	0.2885	benign	-1.202	Destabilizing	0.999	D	0.64	neutral	D	0.558975256	None	None	N
Y/G	0.9891	likely_pathogenic	0.9824	pathogenic	-3.668	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
Y/H	0.9887	likely_pathogenic	0.9759	pathogenic	-2.39	Highly Destabilizing	1.0	D	0.794	deleterious	D	0.646065566	None	None	N
Y/I	0.9738	likely_pathogenic	0.9581	pathogenic	-1.806	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/K	0.9989	likely_pathogenic	0.9981	pathogenic	-2.34	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/L	0.9553	likely_pathogenic	0.9405	pathogenic	-1.806	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
Y/M	0.9779	likely_pathogenic	0.9636	pathogenic	-1.574	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/N	0.9766	likely_pathogenic	0.9571	pathogenic	-3.188	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.646469175	None	None	N
Y/P	0.9995	likely_pathogenic	0.9993	pathogenic	-2.302	Highly Destabilizing	1.0	D	0.94	deleterious	None	None	None	None	N
Y/Q	0.9988	likely_pathogenic	0.9973	pathogenic	-2.905	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.9969	likely_pathogenic	0.9944	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/S	0.9928	likely_pathogenic	0.9858	pathogenic	-3.507	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.646469175	None	None	N
Y/T	0.9947	likely_pathogenic	0.9899	pathogenic	-3.162	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/V	0.959	likely_pathogenic	0.9356	pathogenic	-2.302	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Y/W	0.9219	likely_pathogenic	0.8938	pathogenic	-0.499	Destabilizing	1.0	D	0.786	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.