TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21705	65338;65339;65340	chr2:178584438;178584437;178584436	chr2:179449165;179449164;179449163
N2AB	20064	60415;60416;60417	chr2:178584438;178584437;178584436	chr2:179449165;179449164;179449163
N2A	19137	57634;57635;57636	chr2:178584438;178584437;178584436	chr2:179449165;179449164;179449163
N2B	12640	38143;38144;38145	chr2:178584438;178584437;178584436	chr2:179449165;179449164;179449163
Novex-1	12765	38518;38519;38520	chr2:178584438;178584437;178584436	chr2:179449165;179449164;179449163
Novex-2	12832	38719;38720;38721	chr2:178584438;178584437;178584436	chr2:179449165;179449164;179449163
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: Fn3-45
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6511
• Predicted PPI site: I

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/Q	rs2154179812	None	1.0	N	0.699	0.477	0.808029720589	gnomAD-4.0.0	1.50565E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.9792E-05	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	0.8139	likely_pathogenic	0.7813	pathogenic	-0.664	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
L/C	0.8701	likely_pathogenic	0.8433	pathogenic	-0.692	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
L/D	0.9798	likely_pathogenic	0.974	pathogenic	-0.185	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
L/E	0.8995	likely_pathogenic	0.8774	pathogenic	-0.24	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
L/F	0.5878	likely_pathogenic	0.5492	ambiguous	-0.573	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	I
L/G	0.9324	likely_pathogenic	0.9219	pathogenic	-0.83	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
L/H	0.7274	likely_pathogenic	0.6748	pathogenic	0.062	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
L/I	0.2871	likely_benign	0.2636	benign	-0.327	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	I
L/K	0.7528	likely_pathogenic	0.7142	pathogenic	-0.351	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
L/M	0.3078	likely_benign	0.2808	benign	-0.599	Destabilizing	1.0	D	0.551	neutral	N	0.520655102	None	None	I
L/N	0.8755	likely_pathogenic	0.841	pathogenic	-0.258	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
L/P	0.9523	likely_pathogenic	0.9524	pathogenic	-0.41	Destabilizing	1.0	D	0.744	deleterious	N	0.516729363	None	None	I
L/Q	0.5754	likely_pathogenic	0.4818	ambiguous	-0.411	Destabilizing	1.0	D	0.699	prob.neutral	N	0.488387968	None	None	I
L/R	0.6115	likely_pathogenic	0.538	ambiguous	0.158	Stabilizing	1.0	D	0.703	prob.neutral	N	0.431361249	None	None	I
L/S	0.8819	likely_pathogenic	0.8648	pathogenic	-0.709	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
L/T	0.8037	likely_pathogenic	0.7779	pathogenic	-0.654	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
L/V	0.3719	ambiguous	0.3276	benign	-0.41	Destabilizing	0.999	D	0.538	neutral	N	0.489428118	None	None	I
L/W	0.7681	likely_pathogenic	0.7423	pathogenic	-0.588	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
L/Y	0.7855	likely_pathogenic	0.7477	pathogenic	-0.359	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I

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.