TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14872	44839;44840;44841	chr2:178624666;178624665;178624664	chr2:179489393;179489392;179489391
N2AB	13231	39916;39917;39918	chr2:178624666;178624665;178624664	chr2:179489393;179489392;179489391
N2A	12304	37135;37136;37137	chr2:178624666;178624665;178624664	chr2:179489393;179489392;179489391
N2B	5807	17644;17645;17646	chr2:178624666;178624665;178624664	chr2:179489393;179489392;179489391
Novex-1	5932	18019;18020;18021	chr2:178624666;178624665;178624664	chr2:179489393;179489392;179489391
Novex-2	5999	18220;18221;18222	chr2:178624666;178624665;178624664	chr2:179489393;179489392;179489391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-100
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1102
• 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/M	None	None	0.983	D	0.699	0.454	0.487983534966	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	0.9516	likely_pathogenic	0.9535	pathogenic	-2.824	Highly Destabilizing	0.916	D	0.746	deleterious	None	None	None	None	N
L/C	0.9562	likely_pathogenic	0.9545	pathogenic	-1.964	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9991	pathogenic	-3.581	Highly Destabilizing	0.996	D	0.891	deleterious	None	None	None	None	N
L/E	0.9945	likely_pathogenic	0.9937	pathogenic	-3.289	Highly Destabilizing	0.996	D	0.888	deleterious	None	None	None	None	N
L/F	0.3128	likely_benign	0.2767	benign	-1.745	Destabilizing	0.033	N	0.33	neutral	None	None	None	None	N
L/G	0.9909	likely_pathogenic	0.9903	pathogenic	-3.394	Highly Destabilizing	0.987	D	0.889	deleterious	None	None	None	None	N
L/H	0.9779	likely_pathogenic	0.974	pathogenic	-2.925	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
L/I	0.3776	ambiguous	0.3709	ambiguous	-1.119	Destabilizing	0.845	D	0.595	neutral	None	None	None	None	N
L/K	0.9859	likely_pathogenic	0.9835	pathogenic	-2.319	Highly Destabilizing	0.987	D	0.893	deleterious	None	None	None	None	N
L/M	0.2898	likely_benign	0.2714	benign	-1.081	Destabilizing	0.983	D	0.699	prob.neutral	D	0.597389278	None	None	N
L/N	0.9961	likely_pathogenic	0.9956	pathogenic	-2.904	Highly Destabilizing	0.996	D	0.894	deleterious	None	None	None	None	N
L/P	0.9962	likely_pathogenic	0.995	pathogenic	-1.677	Destabilizing	0.994	D	0.894	deleterious	D	0.787455929	None	None	N
L/Q	0.9738	likely_pathogenic	0.9697	pathogenic	-2.661	Highly Destabilizing	0.994	D	0.899	deleterious	D	0.787455929	None	None	N
L/R	0.9729	likely_pathogenic	0.9682	pathogenic	-2.172	Highly Destabilizing	0.994	D	0.889	deleterious	D	0.787455929	None	None	N
L/S	0.9921	likely_pathogenic	0.9914	pathogenic	-3.489	Highly Destabilizing	0.987	D	0.887	deleterious	None	None	None	None	N
L/T	0.971	likely_pathogenic	0.9715	pathogenic	-3.047	Highly Destabilizing	0.987	D	0.823	deleterious	None	None	None	None	N
L/V	0.5077	ambiguous	0.5044	ambiguous	-1.677	Destabilizing	0.892	D	0.621	neutral	D	0.641474077	None	None	N
L/W	0.8856	likely_pathogenic	0.8464	pathogenic	-2.184	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
L/Y	0.9257	likely_pathogenic	0.9146	pathogenic	-1.924	Destabilizing	0.95	D	0.823	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.