TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17184	51775;51776;51777	chr2:178609873;178609872;178609871	chr2:179474600;179474599;179474598
N2AB	15543	46852;46853;46854	chr2:178609873;178609872;178609871	chr2:179474600;179474599;179474598
N2A	14616	44071;44072;44073	chr2:178609873;178609872;178609871	chr2:179474600;179474599;179474598
N2B	8119	24580;24581;24582	chr2:178609873;178609872;178609871	chr2:179474600;179474599;179474598
Novex-1	8244	24955;24956;24957	chr2:178609873;178609872;178609871	chr2:179474600;179474599;179474598
Novex-2	8311	25156;25157;25158	chr2:178609873;178609872;178609871	chr2:179474600;179474599;179474598
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-13
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0775
• 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
I/M	rs767319592	-1.645	0.934	N	0.623	0.382	0.525613252392	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.94175E-04	None	0	0	0
I/M	rs767319592	-1.645	0.934	N	0.623	0.382	0.525613252392	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
I/M	rs767319592	-1.645	0.934	N	0.623	0.382	0.525613252392	gnomAD-4.0.0	8.05965E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.47968E-07	1.20799E-04	1.60241E-05
I/T	rs752646731	-3.469	0.891	D	0.663	0.489	0.773765334734	gnomAD-2.1.1	5.23E-05	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	2.94175E-04	None	0	2.67E-05	0
I/T	rs752646731	-3.469	0.891	D	0.663	0.489	0.773765334734	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs752646731	-3.469	0.891	D	0.663	0.489	0.773765334734	gnomAD-4.0.0	5.51798E-05	None	None	None	None	N	None	1.33626E-05	0	None	0	4.46349E-05	None	0	0	5.4271E-05	2.19664E-04	3.20482E-05
I/V	rs777442915	-1.901	0.267	N	0.291	0.1	0.313210971179	gnomAD-4.0.0	4.77791E-06	None	None	None	None	N	None	5.67022E-05	0	None	0	0	None	0	0	5.72315E-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
I/A	0.9319	likely_pathogenic	0.9206	pathogenic	-3.232	Highly Destabilizing	0.688	D	0.666	neutral	None	None	None	None	N
I/C	0.9778	likely_pathogenic	0.9745	pathogenic	-2.343	Highly Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9995	pathogenic	-3.799	Highly Destabilizing	0.991	D	0.863	deleterious	None	None	None	None	N
I/E	0.9984	likely_pathogenic	0.9978	pathogenic	-3.508	Highly Destabilizing	0.991	D	0.849	deleterious	None	None	None	None	N
I/F	0.9208	likely_pathogenic	0.911	pathogenic	-1.962	Destabilizing	0.949	D	0.661	neutral	None	None	None	None	N
I/G	0.997	likely_pathogenic	0.9961	pathogenic	-3.761	Highly Destabilizing	0.991	D	0.846	deleterious	None	None	None	None	N
I/H	0.9989	likely_pathogenic	0.9985	pathogenic	-3.27	Highly Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
I/K	0.9973	likely_pathogenic	0.996	pathogenic	-2.626	Highly Destabilizing	0.966	D	0.833	deleterious	D	0.539014362	None	None	N
I/L	0.21	likely_benign	0.218	benign	-1.61	Destabilizing	0.002	N	0.273	neutral	N	0.467748911	None	None	N
I/M	0.5137	ambiguous	0.481	ambiguous	-1.754	Destabilizing	0.934	D	0.623	neutral	N	0.499007191	None	None	N
I/N	0.9957	likely_pathogenic	0.9945	pathogenic	-3.275	Highly Destabilizing	0.991	D	0.868	deleterious	None	None	None	None	N
I/P	0.9938	likely_pathogenic	0.9922	pathogenic	-2.148	Highly Destabilizing	0.991	D	0.87	deleterious	None	None	None	None	N
I/Q	0.9975	likely_pathogenic	0.9967	pathogenic	-2.98	Highly Destabilizing	0.991	D	0.874	deleterious	None	None	None	None	N
I/R	0.9954	likely_pathogenic	0.9936	pathogenic	-2.485	Highly Destabilizing	0.966	D	0.865	deleterious	D	0.539014362	None	None	N
I/S	0.9893	likely_pathogenic	0.9866	pathogenic	-3.762	Highly Destabilizing	0.974	D	0.788	deleterious	None	None	None	None	N
I/T	0.9022	likely_pathogenic	0.8828	pathogenic	-3.337	Highly Destabilizing	0.891	D	0.663	neutral	D	0.538760873	None	None	N
I/V	0.1111	likely_benign	0.1046	benign	-2.148	Highly Destabilizing	0.267	N	0.291	neutral	N	0.427931368	None	None	N
I/W	0.9985	likely_pathogenic	0.9981	pathogenic	-2.301	Highly Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
I/Y	0.9963	likely_pathogenic	0.995	pathogenic	-2.235	Highly Destabilizing	0.974	D	0.761	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.