TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20605	62038;62039;62040	chr2:178589912;178589911;178589910	chr2:179454639;179454638;179454637
N2AB	18964	57115;57116;57117	chr2:178589912;178589911;178589910	chr2:179454639;179454638;179454637
N2A	18037	54334;54335;54336	chr2:178589912;178589911;178589910	chr2:179454639;179454638;179454637
N2B	11540	34843;34844;34845	chr2:178589912;178589911;178589910	chr2:179454639;179454638;179454637
Novex-1	11665	35218;35219;35220	chr2:178589912;178589911;178589910	chr2:179454639;179454638;179454637
Novex-2	11732	35419;35420;35421	chr2:178589912;178589911;178589910	chr2:179454639;179454638;179454637
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-37
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2223
• 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
I/M	rs761374262	-1.546	1.0	N	0.75	0.314	0.613267566169	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.9E-05	0
I/M	rs761374262	-1.546	1.0	N	0.75	0.314	0.613267566169	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
I/M	rs761374262	-1.546	1.0	N	0.75	0.314	0.613267566169	gnomAD-4.0.0	2.6654E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.64535E-05	0	0
I/T	rs140252432	-2.889	1.0	N	0.683	0.395	None	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	1.29216E-04	0	None	0	1.68672E-04	None	0	None	0	0	1.65782E-04
I/T	rs140252432	-2.889	1.0	N	0.683	0.395	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	6.55E-05	0	0	1.93874E-04	None	0	0	0	0	0
I/T	rs140252432	-2.889	1.0	N	0.683	0.395	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	1.4E-03	None	None	1E-03	0	None	None	None	0	None
I/T	rs140252432	-2.889	1.0	N	0.683	0.395	None	gnomAD-4.0.0	7.69038E-06	None	None	None	None	N	None	6.75379E-05	1.6956E-05	None	0	2.43499E-05	None	0	0	0	0	0
I/V	rs759096564	-1.864	0.993	N	0.389	0.229	0.621134785655	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	8.87E-06	0
I/V	rs759096564	-1.864	0.993	N	0.389	0.229	0.621134785655	gnomAD-4.0.0	8.21292E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19692E-06	4.63843E-05	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
I/A	0.8137	likely_pathogenic	0.8032	pathogenic	-2.503	Highly Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
I/C	0.9071	likely_pathogenic	0.9033	pathogenic	-1.845	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
I/D	0.983	likely_pathogenic	0.9801	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
I/E	0.9339	likely_pathogenic	0.9184	pathogenic	-2.779	Highly Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
I/F	0.5164	ambiguous	0.4649	ambiguous	-1.582	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
I/G	0.9786	likely_pathogenic	0.9749	pathogenic	-2.929	Highly Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
I/H	0.8057	likely_pathogenic	0.7756	pathogenic	-2.18	Highly Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
I/K	0.7164	likely_pathogenic	0.6654	pathogenic	-1.935	Destabilizing	1.0	D	0.739	prob.delet.	N	0.519132163	None	None	N
I/L	0.3047	likely_benign	0.2853	benign	-1.31	Destabilizing	0.993	D	0.387	neutral	N	0.510840753	None	None	N
I/M	0.3031	likely_benign	0.2757	benign	-1.208	Destabilizing	1.0	D	0.75	deleterious	N	0.487662614	None	None	N
I/N	0.8108	likely_pathogenic	0.7897	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
I/P	0.9963	likely_pathogenic	0.9948	pathogenic	-1.686	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
I/Q	0.809	likely_pathogenic	0.7541	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
I/R	0.5921	likely_pathogenic	0.531	ambiguous	-1.367	Destabilizing	1.0	D	0.765	deleterious	N	0.467717799	None	None	N
I/S	0.7918	likely_pathogenic	0.7655	pathogenic	-2.66	Highly Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
I/T	0.445	ambiguous	0.4208	ambiguous	-2.43	Highly Destabilizing	1.0	D	0.683	prob.neutral	N	0.504298783	None	None	N
I/V	0.1415	likely_benign	0.1407	benign	-1.686	Destabilizing	0.993	D	0.389	neutral	N	0.46674326	None	None	N
I/W	0.9434	likely_pathogenic	0.9255	pathogenic	-1.857	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
I/Y	0.8265	likely_pathogenic	0.7965	pathogenic	-1.648	Destabilizing	1.0	D	0.739	prob.delet.	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.