TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21514	64765;64766;64767	chr2:178585204;178585203;178585202	chr2:179449931;179449930;179449929
N2AB	19873	59842;59843;59844	chr2:178585204;178585203;178585202	chr2:179449931;179449930;179449929
N2A	18946	57061;57062;57063	chr2:178585204;178585203;178585202	chr2:179449931;179449930;179449929
N2B	12449	37570;37571;37572	chr2:178585204;178585203;178585202	chr2:179449931;179449930;179449929
Novex-1	12574	37945;37946;37947	chr2:178585204;178585203;178585202	chr2:179449931;179449930;179449929
Novex-2	12641	38146;38147;38148	chr2:178585204;178585203;178585202	chr2:179449931;179449930;179449929
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-124
• Domain position: 46
• Structural Position: 122
• Q(SASA): 0.2582
• 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
A/V	rs1060500520	None	0.026	N	0.231	0.142	0.394837016283	gnomAD-4.0.0	2.05314E-06	None	None	None	None	N	None	2.98972E-05	0	None	0	0	None	0	0	1.79937E-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
A/C	0.5462	ambiguous	0.5461	ambiguous	-1.229	Destabilizing	0.999	D	0.486	neutral	None	None	None	None	N
A/D	0.6545	likely_pathogenic	0.5697	pathogenic	-1.772	Destabilizing	0.976	D	0.639	neutral	None	None	None	None	N
A/E	0.538	ambiguous	0.471	ambiguous	-1.723	Destabilizing	0.968	D	0.497	neutral	N	0.443533618	None	None	N
A/F	0.4537	ambiguous	0.4518	ambiguous	-1.036	Destabilizing	0.976	D	0.674	neutral	None	None	None	None	N
A/G	0.3057	likely_benign	0.2681	benign	-1.453	Destabilizing	0.896	D	0.419	neutral	N	0.487383183	None	None	N
A/H	0.6048	likely_pathogenic	0.5794	pathogenic	-1.766	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
A/I	0.3239	likely_benign	0.3055	benign	-0.251	Destabilizing	0.851	D	0.472	neutral	None	None	None	None	N
A/K	0.7723	likely_pathogenic	0.7337	pathogenic	-1.4	Destabilizing	0.976	D	0.502	neutral	None	None	None	None	N
A/L	0.2219	likely_benign	0.2246	benign	-0.251	Destabilizing	0.851	D	0.446	neutral	None	None	None	None	N
A/M	0.2607	likely_benign	0.2805	benign	-0.279	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N
A/N	0.444	ambiguous	0.4202	ambiguous	-1.306	Destabilizing	0.976	D	0.649	neutral	None	None	None	None	N
A/P	0.9124	likely_pathogenic	0.8563	pathogenic	-0.491	Destabilizing	0.984	D	0.589	neutral	N	0.498600254	None	None	N
A/Q	0.5033	ambiguous	0.4858	ambiguous	-1.348	Destabilizing	0.988	D	0.593	neutral	None	None	None	None	N
A/R	0.6961	likely_pathogenic	0.6603	pathogenic	-1.206	Destabilizing	0.988	D	0.594	neutral	None	None	None	None	N
A/S	0.1309	likely_benign	0.123	benign	-1.711	Destabilizing	0.251	N	0.239	neutral	N	0.417867169	None	None	N
A/T	0.1239	likely_benign	0.1142	benign	-1.553	Destabilizing	0.811	D	0.402	neutral	N	0.426084008	None	None	N
A/V	0.1694	likely_benign	0.1594	benign	-0.491	Destabilizing	0.026	N	0.231	neutral	N	0.454366687	None	None	N
A/W	0.8389	likely_pathogenic	0.8365	pathogenic	-1.539	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
A/Y	0.5792	likely_pathogenic	0.5606	ambiguous	-1.084	Destabilizing	0.988	D	0.671	neutral	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.