TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23880	71863;71864;71865	chr2:178574494;178574493;178574492	chr2:179439221;179439220;179439219
N2AB	22239	66940;66941;66942	chr2:178574494;178574493;178574492	chr2:179439221;179439220;179439219
N2A	21312	64159;64160;64161	chr2:178574494;178574493;178574492	chr2:179439221;179439220;179439219
N2B	14815	44668;44669;44670	chr2:178574494;178574493;178574492	chr2:179439221;179439220;179439219
Novex-1	14940	45043;45044;45045	chr2:178574494;178574493;178574492	chr2:179439221;179439220;179439219
Novex-2	15007	45244;45245;45246	chr2:178574494;178574493;178574492	chr2:179439221;179439220;179439219
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-61
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.2826
• 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
L/S	None	None	0.942	N	0.557	0.354	0.465464902746	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.217	likely_benign	0.2013	benign	-1.548	Destabilizing	0.754	D	0.491	neutral	None	None	None	None	N
L/C	0.5176	ambiguous	0.4889	ambiguous	-0.799	Destabilizing	0.092	N	0.411	neutral	None	None	None	None	N
L/D	0.8308	likely_pathogenic	0.808	pathogenic	-1.06	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
L/E	0.5554	ambiguous	0.5342	ambiguous	-1.089	Destabilizing	0.978	D	0.647	neutral	None	None	None	None	N
L/F	0.2109	likely_benign	0.1968	benign	-1.162	Destabilizing	0.032	N	0.251	neutral	N	0.466983784	None	None	N
L/G	0.6268	likely_pathogenic	0.5736	pathogenic	-1.841	Destabilizing	0.978	D	0.619	neutral	None	None	None	None	N
L/H	0.3667	ambiguous	0.3423	ambiguous	-1.089	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
L/I	0.0894	likely_benign	0.0859	benign	-0.83	Destabilizing	0.058	N	0.223	neutral	N	0.45038694	None	None	N
L/K	0.3594	ambiguous	0.3544	ambiguous	-1.041	Destabilizing	0.978	D	0.597	neutral	None	None	None	None	N
L/M	0.125	likely_benign	0.1193	benign	-0.564	Destabilizing	0.978	D	0.569	neutral	None	None	None	None	N
L/N	0.5014	ambiguous	0.4733	ambiguous	-0.758	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
L/P	0.1576	likely_benign	0.1454	benign	-1.038	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
L/Q	0.252	likely_benign	0.2285	benign	-0.985	Destabilizing	0.993	D	0.612	neutral	None	None	None	None	N
L/R	0.2774	likely_benign	0.2589	benign	-0.401	Destabilizing	0.978	D	0.607	neutral	None	None	None	None	N
L/S	0.3658	ambiguous	0.3306	benign	-1.313	Destabilizing	0.942	D	0.557	neutral	N	0.496753948	None	None	N
L/T	0.2296	likely_benign	0.2203	benign	-1.232	Destabilizing	0.86	D	0.493	neutral	None	None	None	None	N
L/V	0.0931	likely_benign	0.0899	benign	-1.038	Destabilizing	0.014	N	0.195	neutral	N	0.465316321	None	None	N
L/W	0.3941	ambiguous	0.3687	ambiguous	-1.212	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	N
L/Y	0.4619	ambiguous	0.4491	ambiguous	-1.008	Destabilizing	0.915	D	0.555	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.