TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15332	46219;46220;46221	chr2:178620527;178620526;178620525	chr2:179485254;179485253;179485252
N2AB	13691	41296;41297;41298	chr2:178620527;178620526;178620525	chr2:179485254;179485253;179485252
N2A	12764	38515;38516;38517	chr2:178620527;178620526;178620525	chr2:179485254;179485253;179485252
N2B	6267	19024;19025;19026	chr2:178620527;178620526;178620525	chr2:179485254;179485253;179485252
Novex-1	6392	19399;19400;19401	chr2:178620527;178620526;178620525	chr2:179485254;179485253;179485252
Novex-2	6459	19600;19601;19602	chr2:178620527;178620526;178620525	chr2:179485254;179485253;179485252
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: Ig-105
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.1308
• 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/M	None	None	0.997	N	0.745	0.253	0.584212540733	gnomAD-4.0.0	6.84812E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00037E-07	0	0
L/P	None	None	0.999	N	0.818	0.77	0.885213830694	gnomAD-4.0.0	1.3696E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80004E-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	0.7724	likely_pathogenic	0.7193	pathogenic	-2.506	Highly Destabilizing	0.966	D	0.657	neutral	None	None	None	None	N
L/C	0.8114	likely_pathogenic	0.7981	pathogenic	-1.648	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/D	0.9981	likely_pathogenic	0.996	pathogenic	-3.158	Highly Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
L/E	0.9854	likely_pathogenic	0.9693	pathogenic	-2.897	Highly Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
L/F	0.7717	likely_pathogenic	0.7134	pathogenic	-1.631	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
L/G	0.9537	likely_pathogenic	0.9374	pathogenic	-3.02	Highly Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
L/H	0.9825	likely_pathogenic	0.965	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/I	0.1765	likely_benign	0.1452	benign	-0.987	Destabilizing	0.921	D	0.585	neutral	None	None	None	None	N
L/K	0.9811	likely_pathogenic	0.9656	pathogenic	-2.012	Highly Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
L/M	0.3116	likely_benign	0.2702	benign	-0.885	Destabilizing	0.997	D	0.745	deleterious	N	0.512298486	None	None	N
L/N	0.9841	likely_pathogenic	0.9715	pathogenic	-2.532	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
L/P	0.9373	likely_pathogenic	0.9008	pathogenic	-1.482	Destabilizing	0.999	D	0.818	deleterious	N	0.514823397	None	None	N
L/Q	0.953	likely_pathogenic	0.9061	pathogenic	-2.34	Highly Destabilizing	0.999	D	0.838	deleterious	N	0.514823397	None	None	N
L/R	0.9688	likely_pathogenic	0.944	pathogenic	-1.876	Destabilizing	0.999	D	0.825	deleterious	N	0.514823397	None	None	N
L/S	0.9614	likely_pathogenic	0.9215	pathogenic	-3.102	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
L/T	0.8032	likely_pathogenic	0.7121	pathogenic	-2.692	Highly Destabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
L/V	0.1289	likely_benign	0.1017	benign	-1.482	Destabilizing	0.117	N	0.348	neutral	N	0.332346474	None	None	N
L/W	0.9753	likely_pathogenic	0.9532	pathogenic	-1.973	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/Y	0.9796	likely_pathogenic	0.969	pathogenic	-1.679	Destabilizing	0.999	D	0.774	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.