TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19349	58270;58271;58272	chr2:178594449;178594448;178594447	chr2:179459176;179459175;179459174
N2AB	17708	53347;53348;53349	chr2:178594449;178594448;178594447	chr2:179459176;179459175;179459174
N2A	16781	50566;50567;50568	chr2:178594449;178594448;178594447	chr2:179459176;179459175;179459174
N2B	10284	31075;31076;31077	chr2:178594449;178594448;178594447	chr2:179459176;179459175;179459174
Novex-1	10409	31450;31451;31452	chr2:178594449;178594448;178594447	chr2:179459176;179459175;179459174
Novex-2	10476	31651;31652;31653	chr2:178594449;178594448;178594447	chr2:179459176;179459175;179459174
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: Fn3-28
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1396
• 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/F	None	None	1.0	D	0.867	0.683	0.789146157882	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.8959	likely_pathogenic	0.8723	pathogenic	-2.292	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/C	0.7597	likely_pathogenic	0.7482	pathogenic	-1.643	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/D	0.9974	likely_pathogenic	0.9968	pathogenic	-1.913	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/E	0.9745	likely_pathogenic	0.9637	pathogenic	-1.851	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.7499	likely_pathogenic	0.6995	pathogenic	-1.663	Destabilizing	1.0	D	0.867	deleterious	D	0.61250703	None	None	N
L/G	0.9713	likely_pathogenic	0.966	pathogenic	-2.697	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/H	0.9414	likely_pathogenic	0.9256	pathogenic	-1.832	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/I	0.3326	likely_benign	0.2892	benign	-1.201	Destabilizing	0.999	D	0.775	deleterious	D	0.614283985	None	None	N
L/K	0.9392	likely_pathogenic	0.9183	pathogenic	-1.616	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/M	0.352	ambiguous	0.3086	benign	-0.963	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/N	0.9586	likely_pathogenic	0.9539	pathogenic	-1.553	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/P	0.9876	likely_pathogenic	0.9867	pathogenic	-1.537	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/Q	0.848	likely_pathogenic	0.7936	pathogenic	-1.694	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/R	0.9037	likely_pathogenic	0.8766	pathogenic	-0.983	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/S	0.9754	likely_pathogenic	0.9664	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.664390471	None	None	N
L/T	0.9103	likely_pathogenic	0.8869	pathogenic	-2.076	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/V	0.3615	ambiguous	0.2997	benign	-1.537	Destabilizing	0.999	D	0.788	deleterious	D	0.581427327	None	None	N
L/W	0.9529	likely_pathogenic	0.9364	pathogenic	-1.761	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/Y	0.9549	likely_pathogenic	0.9446	pathogenic	-1.556	Destabilizing	1.0	D	0.882	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.