TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29614	89065;89066;89067	chr2:178554507;178554506;178554505	chr2:179419234;179419233;179419232
N2AB	27973	84142;84143;84144	chr2:178554507;178554506;178554505	chr2:179419234;179419233;179419232
N2A	27046	81361;81362;81363	chr2:178554507;178554506;178554505	chr2:179419234;179419233;179419232
N2B	20549	61870;61871;61872	chr2:178554507;178554506;178554505	chr2:179419234;179419233;179419232
Novex-1	20674	62245;62246;62247	chr2:178554507;178554506;178554505	chr2:179419234;179419233;179419232
Novex-2	20741	62446;62447;62448	chr2:178554507;178554506;178554505	chr2:179419234;179419233;179419232
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: Fn3-103
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.657
• 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
Y/C	rs770430100	0.319	0.999	N	0.623	0.32	0.507987536778	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
Y/C	rs770430100	0.319	0.999	N	0.623	0.32	0.507987536778	gnomAD-4.0.0	1.59249E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85897E-06	0	0
Y/H	None	None	0.059	N	0.297	0.182	0.247872288689	gnomAD-4.0.0	1.5924E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85887E-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	0.8869	likely_pathogenic	0.9045	pathogenic	-0.526	Destabilizing	0.919	D	0.588	neutral	None	None	None	None	I
Y/C	0.433	ambiguous	0.5192	ambiguous	0.181	Stabilizing	0.999	D	0.623	neutral	N	0.48925476	None	None	I
Y/D	0.862	likely_pathogenic	0.8603	pathogenic	0.839	Stabilizing	0.938	D	0.565	neutral	N	0.473758187	None	None	I
Y/E	0.9528	likely_pathogenic	0.9529	pathogenic	0.814	Stabilizing	0.976	D	0.561	neutral	None	None	None	None	I
Y/F	0.0958	likely_benign	0.0927	benign	-0.288	Destabilizing	0.026	N	0.329	neutral	N	0.469148847	None	None	I
Y/G	0.8954	likely_pathogenic	0.9098	pathogenic	-0.703	Destabilizing	0.919	D	0.595	neutral	None	None	None	None	I
Y/H	0.5054	ambiguous	0.4944	ambiguous	0.282	Stabilizing	0.059	N	0.297	neutral	N	0.513977059	None	None	I
Y/I	0.7035	likely_pathogenic	0.7174	pathogenic	-0.093	Destabilizing	0.952	D	0.528	neutral	None	None	None	None	I
Y/K	0.9581	likely_pathogenic	0.9584	pathogenic	0.29	Stabilizing	0.976	D	0.559	neutral	None	None	None	None	I
Y/L	0.7559	likely_pathogenic	0.777	pathogenic	-0.093	Destabilizing	0.851	D	0.538	neutral	None	None	None	None	I
Y/M	0.7948	likely_pathogenic	0.8005	pathogenic	-0.025	Destabilizing	0.997	D	0.537	neutral	None	None	None	None	I
Y/N	0.596	likely_pathogenic	0.5967	pathogenic	0.098	Stabilizing	0.059	N	0.441	neutral	N	0.509512602	None	None	I
Y/P	0.9882	likely_pathogenic	0.9896	pathogenic	-0.218	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	I
Y/Q	0.912	likely_pathogenic	0.9172	pathogenic	0.139	Stabilizing	0.988	D	0.547	neutral	None	None	None	None	I
Y/R	0.9206	likely_pathogenic	0.9233	pathogenic	0.51	Stabilizing	0.976	D	0.596	neutral	None	None	None	None	I
Y/S	0.7802	likely_pathogenic	0.8041	pathogenic	-0.287	Destabilizing	0.811	D	0.581	neutral	N	0.486867816	None	None	I
Y/T	0.891	likely_pathogenic	0.9031	pathogenic	-0.22	Destabilizing	0.976	D	0.553	neutral	None	None	None	None	I
Y/V	0.6579	likely_pathogenic	0.6993	pathogenic	-0.218	Destabilizing	0.919	D	0.55	neutral	None	None	None	None	I
Y/W	0.5343	ambiguous	0.5408	ambiguous	-0.457	Destabilizing	0.999	D	0.455	neutral	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.