TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27124	81595;81596;81597	chr2:178564762;178564761;178564760	chr2:179429489;179429488;179429487
N2AB	25483	76672;76673;76674	chr2:178564762;178564761;178564760	chr2:179429489;179429488;179429487
N2A	24556	73891;73892;73893	chr2:178564762;178564761;178564760	chr2:179429489;179429488;179429487
N2B	18059	54400;54401;54402	chr2:178564762;178564761;178564760	chr2:179429489;179429488;179429487
Novex-1	18184	54775;54776;54777	chr2:178564762;178564761;178564760	chr2:179429489;179429488;179429487
Novex-2	18251	54976;54977;54978	chr2:178564762;178564761;178564760	chr2:179429489;179429488;179429487
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-85
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.9361
• 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
K/N	None	None	0.884	N	0.361	0.144	0.228597637076	gnomAD-4.0.0	6.84961E-07	None	None	None	None	I	None	2.99168E-05	0	None	0	0	None	0	0	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
K/A	0.6379	likely_pathogenic	0.6315	pathogenic	0.007	Stabilizing	0.998	D	0.544	neutral	None	None	None	None	I
K/C	0.8469	likely_pathogenic	0.8425	pathogenic	-0.408	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
K/D	0.755	likely_pathogenic	0.7392	pathogenic	-0.249	Destabilizing	0.998	D	0.522	neutral	None	None	None	None	I
K/E	0.4935	ambiguous	0.4774	ambiguous	-0.27	Destabilizing	0.996	D	0.543	neutral	N	0.498084887	None	None	I
K/F	0.9363	likely_pathogenic	0.9393	pathogenic	-0.365	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
K/G	0.6591	likely_pathogenic	0.6465	pathogenic	-0.106	Destabilizing	0.997	D	0.49	neutral	None	None	None	None	I
K/H	0.4487	ambiguous	0.442	ambiguous	-0.228	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	I
K/I	0.7111	likely_pathogenic	0.737	pathogenic	0.22	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	I
K/L	0.6901	likely_pathogenic	0.6945	pathogenic	0.22	Stabilizing	1.0	D	0.489	neutral	None	None	None	None	I
K/M	0.5698	likely_pathogenic	0.577	pathogenic	-0.065	Destabilizing	1.0	D	0.595	neutral	N	0.485763283	None	None	I
K/N	0.6468	likely_pathogenic	0.6453	pathogenic	0.059	Stabilizing	0.884	D	0.361	neutral	N	0.506165652	None	None	I
K/P	0.7699	likely_pathogenic	0.7531	pathogenic	0.172	Stabilizing	1.0	D	0.569	neutral	None	None	None	None	I
K/Q	0.2663	likely_benign	0.2529	benign	-0.096	Destabilizing	0.999	D	0.621	neutral	N	0.472836815	None	None	I
K/R	0.0863	likely_benign	0.0853	benign	-0.098	Destabilizing	0.998	D	0.551	neutral	N	0.497372811	None	None	I
K/S	0.6582	likely_pathogenic	0.637	pathogenic	-0.313	Destabilizing	0.997	D	0.548	neutral	None	None	None	None	I
K/T	0.4003	ambiguous	0.3954	ambiguous	-0.223	Destabilizing	0.999	D	0.54	neutral	N	0.49521794	None	None	I
K/V	0.6556	likely_pathogenic	0.6673	pathogenic	0.172	Stabilizing	1.0	D	0.562	neutral	None	None	None	None	I
K/W	0.8962	likely_pathogenic	0.8964	pathogenic	-0.466	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
K/Y	0.8139	likely_pathogenic	0.8223	pathogenic	-0.112	Destabilizing	1.0	D	0.591	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.