TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16074	48445;48446;48447	chr2:178616571;178616570;178616569	chr2:179481298;179481297;179481296
N2AB	14433	43522;43523;43524	chr2:178616571;178616570;178616569	chr2:179481298;179481297;179481296
N2A	13506	40741;40742;40743	chr2:178616571;178616570;178616569	chr2:179481298;179481297;179481296
N2B	7009	21250;21251;21252	chr2:178616571;178616570;178616569	chr2:179481298;179481297;179481296
Novex-1	7134	21625;21626;21627	chr2:178616571;178616570;178616569	chr2:179481298;179481297;179481296
Novex-2	7201	21826;21827;21828	chr2:178616571;178616570;178616569	chr2:179481298;179481297;179481296
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-4
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0776
• 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	rs1285719180	-1.656	1.0	D	0.719	0.487	0.607129708303	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
L/F	rs1285719180	-1.656	1.0	D	0.719	0.487	0.607129708303	gnomAD-4.0.0	6.84733E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73853E-04	0	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	0.9478	likely_pathogenic	0.9529	pathogenic	-2.706	Highly Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
L/C	0.8507	likely_pathogenic	0.8817	pathogenic	-1.726	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.292	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/E	0.9973	likely_pathogenic	0.9966	pathogenic	-2.967	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/F	0.448	ambiguous	0.4666	ambiguous	-1.63	Destabilizing	1.0	D	0.719	prob.delet.	D	0.713124516	None	None	N
L/G	0.9922	likely_pathogenic	0.9916	pathogenic	-3.287	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/H	0.9915	likely_pathogenic	0.9899	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/I	0.1072	likely_benign	0.1248	benign	-0.93	Destabilizing	0.999	D	0.549	neutral	None	None	None	None	N
L/K	0.9947	likely_pathogenic	0.9931	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/M	0.2116	likely_benign	0.2331	benign	-1.179	Destabilizing	1.0	D	0.707	prob.neutral	D	0.676533383	None	None	N
L/N	0.9976	likely_pathogenic	0.9972	pathogenic	-2.811	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/P	0.9975	likely_pathogenic	0.9966	pathogenic	-1.519	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/Q	0.9876	likely_pathogenic	0.984	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/R	0.9894	likely_pathogenic	0.987	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/S	0.9942	likely_pathogenic	0.9938	pathogenic	-3.227	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.798073427	None	None	N
L/T	0.97	likely_pathogenic	0.9727	pathogenic	-2.739	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/V	0.1574	likely_benign	0.1887	benign	-1.519	Destabilizing	0.999	D	0.564	neutral	N	0.488419852	None	None	N
L/W	0.9571	likely_pathogenic	0.952	pathogenic	-1.906	Destabilizing	1.0	D	0.849	deleterious	D	0.798073427	None	None	N
L/Y	0.9624	likely_pathogenic	0.9658	pathogenic	-1.823	Destabilizing	1.0	D	0.819	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.