TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15952	48079;48080;48081	chr2:178617141;178617140;178617139	chr2:179481868;179481867;179481866
N2AB	14311	43156;43157;43158	chr2:178617141;178617140;178617139	chr2:179481868;179481867;179481866
N2A	13384	40375;40376;40377	chr2:178617141;178617140;178617139	chr2:179481868;179481867;179481866
N2B	6887	20884;20885;20886	chr2:178617141;178617140;178617139	chr2:179481868;179481867;179481866
Novex-1	7012	21259;21260;21261	chr2:178617141;178617140;178617139	chr2:179481868;179481867;179481866
Novex-2	7079	21460;21461;21462	chr2:178617141;178617140;178617139	chr2:179481868;179481867;179481866
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-3
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.1674
• 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/P	None	None	0.999	D	0.876	0.437	0.731863806485	gnomAD-4.0.0	1.20046E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07607E-05	0
L/V	rs2057492461	None	0.429	N	0.347	0.114	0.18995819373	gnomAD-4.0.0	1.37272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80263E-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	0.4644	ambiguous	0.4614	ambiguous	-2.355	Highly Destabilizing	0.987	D	0.691	prob.delet.	None	None	None	None	N
L/C	0.5802	likely_pathogenic	0.5875	pathogenic	-1.45	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/D	0.9076	likely_pathogenic	0.9112	pathogenic	-2.384	Highly Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
L/E	0.5511	ambiguous	0.5548	ambiguous	-2.208	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
L/F	0.2445	likely_benign	0.2251	benign	-1.409	Destabilizing	0.998	D	0.811	deleterious	N	0.477689691	None	None	N
L/G	0.8415	likely_pathogenic	0.8432	pathogenic	-2.851	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/H	0.4559	ambiguous	0.4455	ambiguous	-2.136	Highly Destabilizing	1.0	D	0.883	deleterious	N	0.436068506	None	None	N
L/I	0.097	likely_benign	0.098	benign	-0.952	Destabilizing	0.966	D	0.647	neutral	N	0.432701484	None	None	N
L/K	0.4207	ambiguous	0.4238	ambiguous	-1.875	Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
L/M	0.1371	likely_benign	0.138	benign	-0.717	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
L/N	0.7062	likely_pathogenic	0.7063	pathogenic	-2.056	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/P	0.9302	likely_pathogenic	0.9271	pathogenic	-1.397	Destabilizing	0.999	D	0.876	deleterious	D	0.523165899	None	None	N
L/Q	0.2747	likely_benign	0.2731	benign	-2.009	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/R	0.3747	ambiguous	0.3671	ambiguous	-1.435	Destabilizing	0.999	D	0.896	deleterious	N	0.515912859	None	None	N
L/S	0.5971	likely_pathogenic	0.5963	pathogenic	-2.74	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
L/T	0.4167	ambiguous	0.4317	ambiguous	-2.428	Highly Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
L/V	0.0913	likely_benign	0.0955	benign	-1.397	Destabilizing	0.429	N	0.347	neutral	N	0.420447931	None	None	N
L/W	0.5891	likely_pathogenic	0.5617	ambiguous	-1.736	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/Y	0.5767	likely_pathogenic	0.5504	ambiguous	-1.452	Destabilizing	0.999	D	0.853	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.