TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23942	72049;72050;72051	chr2:178574308;178574307;178574306	chr2:179439035;179439034;179439033
N2AB	22301	67126;67127;67128	chr2:178574308;178574307;178574306	chr2:179439035;179439034;179439033
N2A	21374	64345;64346;64347	chr2:178574308;178574307;178574306	chr2:179439035;179439034;179439033
N2B	14877	44854;44855;44856	chr2:178574308;178574307;178574306	chr2:179439035;179439034;179439033
Novex-1	15002	45229;45230;45231	chr2:178574308;178574307;178574306	chr2:179439035;179439034;179439033
Novex-2	15069	45430;45431;45432	chr2:178574308;178574307;178574306	chr2:179439035;179439034;179439033
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-62
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.192
• 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
T/I	None	None	0.062	N	0.615	0.246	0.304760801415	gnomAD-4.0.0	6.84317E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65667E-05
T/K	None	None	0.062	N	0.589	0.305	0.282575091529	gnomAD-4.0.0	6.84317E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15955E-05	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
T/A	0.1051	likely_benign	0.1173	benign	-0.988	Destabilizing	None	N	0.246	neutral	N	0.476612705	None	None	N
T/C	0.4834	ambiguous	0.4885	ambiguous	-0.953	Destabilizing	0.824	D	0.588	neutral	None	None	None	None	N
T/D	0.5412	ambiguous	0.5643	pathogenic	-1.615	Destabilizing	0.081	N	0.602	neutral	None	None	None	None	N
T/E	0.4689	ambiguous	0.485	ambiguous	-1.491	Destabilizing	0.149	N	0.59	neutral	None	None	None	None	N
T/F	0.337	likely_benign	0.3668	ambiguous	-0.723	Destabilizing	0.38	N	0.632	neutral	None	None	None	None	N
T/G	0.3636	ambiguous	0.3643	ambiguous	-1.343	Destabilizing	0.081	N	0.591	neutral	None	None	None	None	N
T/H	0.3119	likely_benign	0.328	benign	-1.556	Destabilizing	0.824	D	0.599	neutral	None	None	None	None	N
T/I	0.2282	likely_benign	0.2471	benign	-0.089	Destabilizing	0.062	N	0.615	neutral	N	0.487564163	None	None	N
T/K	0.3024	likely_benign	0.3105	benign	-0.882	Destabilizing	0.062	N	0.589	neutral	N	0.517462868	None	None	N
T/L	0.1393	likely_benign	0.1563	benign	-0.089	Destabilizing	0.001	N	0.399	neutral	None	None	None	None	N
T/M	0.1049	likely_benign	0.1097	benign	-0.022	Destabilizing	0.38	N	0.603	neutral	None	None	None	None	N
T/N	0.1647	likely_benign	0.1785	benign	-1.344	Destabilizing	0.001	N	0.417	neutral	None	None	None	None	N
T/P	0.6867	likely_pathogenic	0.7245	pathogenic	-0.357	Destabilizing	0.317	N	0.633	neutral	N	0.517380345	None	None	N
T/Q	0.2936	likely_benign	0.3015	benign	-1.319	Destabilizing	0.38	N	0.643	neutral	None	None	None	None	N
T/R	0.2584	likely_benign	0.2734	benign	-0.844	Destabilizing	0.317	N	0.639	neutral	N	0.491741219	None	None	N
T/S	0.1184	likely_benign	0.124	benign	-1.487	Destabilizing	0.002	N	0.407	neutral	N	0.476306892	None	None	N
T/V	0.1903	likely_benign	0.1993	benign	-0.357	Destabilizing	0.081	N	0.549	neutral	None	None	None	None	N
T/W	0.7113	likely_pathogenic	0.7369	pathogenic	-0.831	Destabilizing	0.935	D	0.637	neutral	None	None	None	None	N
T/Y	0.3675	ambiguous	0.3882	ambiguous	-0.495	Destabilizing	0.555	D	0.612	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.