TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24010	72253;72254;72255	chr2:178574104;178574103;178574102	chr2:179438831;179438830;179438829
N2AB	22369	67330;67331;67332	chr2:178574104;178574103;178574102	chr2:179438831;179438830;179438829
N2A	21442	64549;64550;64551	chr2:178574104;178574103;178574102	chr2:179438831;179438830;179438829
N2B	14945	45058;45059;45060	chr2:178574104;178574103;178574102	chr2:179438831;179438830;179438829
Novex-1	15070	45433;45434;45435	chr2:178574104;178574103;178574102	chr2:179438831;179438830;179438829
Novex-2	15137	45634;45635;45636	chr2:178574104;178574103;178574102	chr2:179438831;179438830;179438829
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-62
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.4085
• 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/Q	None	None	0.003	N	0.215	0.116	0.255777322467	gnomAD-4.0.0	6.84288E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65667E-05
P/T	None	None	0.183	N	0.428	0.085	0.242825505644	gnomAD-4.0.0	6.84281E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65667E-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	0.0623	likely_benign	0.0666	benign	-1.245	Destabilizing	None	N	0.21	neutral	N	0.43513506	None	None	N
P/C	0.3323	likely_benign	0.3695	ambiguous	-0.84	Destabilizing	0.951	D	0.537	neutral	None	None	None	None	N
P/D	0.3159	likely_benign	0.3382	benign	-1.001	Destabilizing	0.228	N	0.437	neutral	None	None	None	None	N
P/E	0.1479	likely_benign	0.1679	benign	-1.064	Destabilizing	0.129	N	0.372	neutral	None	None	None	None	N
P/F	0.2641	likely_benign	0.3173	benign	-1.124	Destabilizing	0.836	D	0.58	neutral	None	None	None	None	N
P/G	0.2227	likely_benign	0.2441	benign	-1.482	Destabilizing	0.129	N	0.433	neutral	None	None	None	None	N
P/H	0.115	likely_benign	0.1278	benign	-0.954	Destabilizing	0.002	N	0.403	neutral	None	None	None	None	N
P/I	0.1584	likely_benign	0.1797	benign	-0.727	Destabilizing	0.418	N	0.642	neutral	None	None	None	None	N
P/K	0.1271	likely_benign	0.1392	benign	-1.044	Destabilizing	None	N	0.203	neutral	None	None	None	None	N
P/L	0.0631	likely_benign	0.0726	benign	-0.727	Destabilizing	0.101	N	0.439	neutral	N	0.474328167	None	None	N
P/M	0.1616	likely_benign	0.1807	benign	-0.52	Destabilizing	0.94	D	0.557	neutral	None	None	None	None	N
P/N	0.1854	likely_benign	0.2025	benign	-0.77	Destabilizing	0.418	N	0.513	neutral	None	None	None	None	N
P/Q	0.0773	likely_benign	0.0892	benign	-1.025	Destabilizing	0.003	N	0.215	neutral	N	0.473288017	None	None	N
P/R	0.104	likely_benign	0.1188	benign	-0.423	Destabilizing	0.101	N	0.443	neutral	N	0.452451385	None	None	N
P/S	0.0857	likely_benign	0.095	benign	-1.221	Destabilizing	0.101	N	0.414	neutral	N	0.501013336	None	None	N
P/T	0.0837	likely_benign	0.0913	benign	-1.185	Destabilizing	0.183	N	0.428	neutral	N	0.46949835	None	None	N
P/V	0.1185	likely_benign	0.1305	benign	-0.864	Destabilizing	0.129	N	0.442	neutral	None	None	None	None	N
P/W	0.4529	ambiguous	0.5173	ambiguous	-1.216	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
P/Y	0.2497	likely_benign	0.2799	benign	-0.957	Destabilizing	0.418	N	0.645	neutral	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.