TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17721	53386;53387;53388	chr2:178607527;178607526;178607525	chr2:179472254;179472253;179472252
N2AB	16080	48463;48464;48465	chr2:178607527;178607526;178607525	chr2:179472254;179472253;179472252
N2A	15153	45682;45683;45684	chr2:178607527;178607526;178607525	chr2:179472254;179472253;179472252
N2B	8656	26191;26192;26193	chr2:178607527;178607526;178607525	chr2:179472254;179472253;179472252
Novex-1	8781	26566;26567;26568	chr2:178607527;178607526;178607525	chr2:179472254;179472253;179472252
Novex-2	8848	26767;26768;26769	chr2:178607527;178607526;178607525	chr2:179472254;179472253;179472252
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-113
• Domain position: 45
• Structural Position: 125
• Q(SASA): 0.5907
• 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
D/V	None	None	0.012	N	0.376	0.198	0.432826170204	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1332	likely_benign	0.1262	benign	-0.336	Destabilizing	0.012	N	0.34	neutral	N	0.481494573	None	None	N
D/C	0.4767	ambiguous	0.4553	ambiguous	0.034	Stabilizing	0.864	D	0.369	neutral	None	None	None	None	N
D/E	0.0781	likely_benign	0.0707	benign	-0.395	Destabilizing	None	N	0.14	neutral	N	0.395491742	None	None	N
D/F	0.5173	ambiguous	0.5059	ambiguous	-0.291	Destabilizing	0.214	N	0.401	neutral	None	None	None	None	N
D/G	0.1633	likely_benign	0.1718	benign	-0.552	Destabilizing	0.055	N	0.329	neutral	N	0.501467201	None	None	N
D/H	0.1918	likely_benign	0.1733	benign	-0.278	Destabilizing	0.295	N	0.375	neutral	N	0.503814073	None	None	N
D/I	0.2241	likely_benign	0.2274	benign	0.188	Stabilizing	0.038	N	0.407	neutral	None	None	None	None	N
D/K	0.1963	likely_benign	0.1853	benign	0.229	Stabilizing	0.016	N	0.332	neutral	None	None	None	None	N
D/L	0.2489	likely_benign	0.2499	benign	0.188	Stabilizing	None	N	0.235	neutral	None	None	None	None	N
D/M	0.4406	ambiguous	0.439	ambiguous	0.388	Stabilizing	0.214	N	0.389	neutral	None	None	None	None	N
D/N	0.0808	likely_benign	0.0789	benign	-0.068	Destabilizing	0.055	N	0.205	neutral	N	0.485054953	None	None	N
D/P	0.8398	likely_pathogenic	0.8532	pathogenic	0.036	Stabilizing	0.136	N	0.367	neutral	None	None	None	None	N
D/Q	0.1725	likely_benign	0.1546	benign	-0.033	Destabilizing	0.038	N	0.171	neutral	None	None	None	None	N
D/R	0.2393	likely_benign	0.2244	benign	0.346	Stabilizing	0.038	N	0.394	neutral	None	None	None	None	N
D/S	0.101	likely_benign	0.0991	benign	-0.181	Destabilizing	0.016	N	0.233	neutral	None	None	None	None	N
D/T	0.1502	likely_benign	0.1426	benign	-0.014	Destabilizing	0.001	N	0.17	neutral	None	None	None	None	N
D/V	0.132	likely_benign	0.1315	benign	0.036	Stabilizing	0.012	N	0.376	neutral	N	0.472221729	None	None	N
D/W	0.7973	likely_pathogenic	0.7852	pathogenic	-0.162	Destabilizing	0.864	D	0.401	neutral	None	None	None	None	N
D/Y	0.2013	likely_benign	0.1974	benign	-0.057	Destabilizing	0.56	D	0.399	neutral	N	0.499659047	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.