TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8971	27136;27137;27138	chr2:178713223;178713222;178713221	chr2:179577950;179577949;179577948
N2AB	8654	26185;26186;26187	chr2:178713223;178713222;178713221	chr2:179577950;179577949;179577948
N2A	7727	23404;23405;23406	chr2:178713223;178713222;178713221	chr2:179577950;179577949;179577948
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-75
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.4443
• 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
K/E	rs373877046	0.218	0.92	N	0.364	0.257	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/E	rs373877046	0.218	0.92	N	0.364	0.257	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs373877046	0.218	0.92	N	0.364	0.257	None	gnomAD-4.0.0	1.98335E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71257E-05	0	0
K/N	None	None	0.061	N	0.126	0.123	0.0611884634855	gnomAD-4.0.0	2.73724E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59811E-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
K/A	0.824	likely_pathogenic	0.86	pathogenic	-0.601	Destabilizing	0.939	D	0.321	neutral	None	None	None	None	N
K/C	0.9414	likely_pathogenic	0.955	pathogenic	-0.589	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
K/D	0.862	likely_pathogenic	0.8878	pathogenic	0.078	Stabilizing	0.884	D	0.323	neutral	None	None	None	None	N
K/E	0.5852	likely_pathogenic	0.6571	pathogenic	0.182	Stabilizing	0.92	D	0.364	neutral	N	0.509485598	None	None	N
K/F	0.9453	likely_pathogenic	0.9569	pathogenic	-0.427	Destabilizing	0.997	D	0.529	neutral	None	None	None	None	N
K/G	0.8608	likely_pathogenic	0.8755	pathogenic	-0.935	Destabilizing	0.939	D	0.342	neutral	None	None	None	None	N
K/H	0.6011	likely_pathogenic	0.639	pathogenic	-1.202	Destabilizing	0.991	D	0.43	neutral	None	None	None	None	N
K/I	0.6807	likely_pathogenic	0.7513	pathogenic	0.251	Stabilizing	0.996	D	0.513	neutral	N	0.458707535	None	None	N
K/L	0.7072	likely_pathogenic	0.7469	pathogenic	0.251	Stabilizing	0.939	D	0.399	neutral	None	None	None	None	N
K/M	0.5617	ambiguous	0.6447	pathogenic	0.077	Stabilizing	0.999	D	0.428	neutral	None	None	None	None	N
K/N	0.7184	likely_pathogenic	0.7502	pathogenic	-0.336	Destabilizing	0.061	N	0.126	neutral	N	0.47933605	None	None	N
K/P	0.9235	likely_pathogenic	0.9265	pathogenic	-0.003	Destabilizing	0.997	D	0.422	neutral	None	None	None	None	N
K/Q	0.4053	ambiguous	0.4844	ambiguous	-0.381	Destabilizing	0.92	D	0.427	neutral	N	0.507946803	None	None	N
K/R	0.1283	likely_benign	0.1514	benign	-0.401	Destabilizing	0.035	N	0.231	neutral	N	0.364967607	None	None	N
K/S	0.8486	likely_pathogenic	0.8652	pathogenic	-1.007	Destabilizing	0.939	D	0.318	neutral	None	None	None	None	N
K/T	0.5603	ambiguous	0.6269	pathogenic	-0.691	Destabilizing	0.92	D	0.333	neutral	N	0.497095091	None	None	N
K/V	0.7107	likely_pathogenic	0.7754	pathogenic	-0.003	Destabilizing	0.991	D	0.409	neutral	None	None	None	None	N
K/W	0.9249	likely_pathogenic	0.9388	pathogenic	-0.309	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
K/Y	0.8436	likely_pathogenic	0.8712	pathogenic	-0.012	Destabilizing	0.997	D	0.471	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.