TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9477	28654;28655;28656	chr2:178710668;178710667;178710666	chr2:179575395;179575394;179575393
N2AB	9160	27703;27704;27705	chr2:178710668;178710667;178710666	chr2:179575395;179575394;179575393
N2A	8233	24922;24923;24924	chr2:178710668;178710667;178710666	chr2:179575395;179575394;179575393
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-80
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.7319
• 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/E	None	None	0.008	None	0.258	0.192	0.301789629655	gnomAD-4.0.0	1.20032E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-05	0	0
K/R	None	None	0.722	None	0.552	0.202	0.349647731962	gnomAD-4.0.0	3.18772E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.94118E-04	2.85919E-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	0.5607	ambiguous	0.5285	ambiguous	0.016	Stabilizing	0.415	N	0.599	neutral	None	None	None	None	I
K/C	0.9049	likely_pathogenic	0.9126	pathogenic	-0.251	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	I
K/D	0.7266	likely_pathogenic	0.7552	pathogenic	-0.007	Destabilizing	0.633	D	0.617	neutral	None	None	None	None	I
K/E	0.2117	likely_benign	0.1778	benign	0.005	Stabilizing	0.008	N	0.258	neutral	None	None	None	None	I
K/F	0.8919	likely_pathogenic	0.8945	pathogenic	-0.134	Destabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	I
K/G	0.6456	likely_pathogenic	0.6564	pathogenic	-0.195	Destabilizing	0.775	D	0.62	neutral	None	None	None	None	I
K/H	0.4657	ambiguous	0.5008	ambiguous	-0.425	Destabilizing	0.989	D	0.615	neutral	None	None	None	None	I
K/I	0.6059	likely_pathogenic	0.5772	pathogenic	0.494	Stabilizing	0.949	D	0.665	neutral	None	None	None	None	I
K/L	0.6091	likely_pathogenic	0.6166	pathogenic	0.494	Stabilizing	0.775	D	0.59	neutral	None	None	None	None	I
K/M	0.3758	ambiguous	0.3605	ambiguous	0.217	Stabilizing	0.996	D	0.621	neutral	None	None	None	None	I
K/N	0.5311	ambiguous	0.5488	ambiguous	0.166	Stabilizing	0.722	D	0.583	neutral	None	None	None	None	I
K/P	0.9345	likely_pathogenic	0.9513	pathogenic	0.363	Stabilizing	0.961	D	0.608	neutral	None	None	None	None	I
K/Q	0.1792	likely_benign	0.171	benign	-0.006	Destabilizing	0.82	D	0.591	neutral	None	None	None	None	I
K/R	0.0977	likely_benign	0.102	benign	-0.067	Destabilizing	0.722	D	0.552	neutral	None	None	None	None	I
K/S	0.5224	ambiguous	0.4968	ambiguous	-0.31	Destabilizing	0.118	N	0.226	neutral	None	None	None	None	I
K/T	0.2813	likely_benign	0.2401	benign	-0.149	Destabilizing	0.565	D	0.629	neutral	None	None	None	None	I
K/V	0.5616	ambiguous	0.5316	ambiguous	0.363	Stabilizing	0.923	D	0.584	neutral	None	None	None	None	I
K/W	0.8787	likely_pathogenic	0.8849	pathogenic	-0.143	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	I
K/Y	0.7882	likely_pathogenic	0.8118	pathogenic	0.201	Stabilizing	0.987	D	0.673	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.