TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9079	27460;27461;27462	chr2:178712790;178712789;178712788	chr2:179577517;179577516;179577515
N2AB	8762	26509;26510;26511	chr2:178712790;178712789;178712788	chr2:179577517;179577516;179577515
N2A	7835	23728;23729;23730	chr2:178712790;178712789;178712788	chr2:179577517;179577516;179577515
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-76
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2917
• 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
F/I	None	None	0.473	N	0.289	0.122	0.325263233342	gnomAD-4.0.0	1.36844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	8.9947E-07	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
F/A	0.4242	ambiguous	0.3511	ambiguous	-2.068	Highly Destabilizing	0.329	N	0.405	neutral	None	None	None	None	N
F/C	0.4122	ambiguous	0.3475	ambiguous	-0.542	Destabilizing	0.993	D	0.437	neutral	N	0.496479657	None	None	N
F/D	0.6336	likely_pathogenic	0.574	pathogenic	-0.883	Destabilizing	0.007	N	0.249	neutral	None	None	None	None	N
F/E	0.6812	likely_pathogenic	0.6129	pathogenic	-0.867	Destabilizing	0.543	D	0.491	neutral	None	None	None	None	N
F/G	0.6667	likely_pathogenic	0.5907	pathogenic	-2.357	Highly Destabilizing	0.495	N	0.455	neutral	None	None	None	None	N
F/H	0.4044	ambiguous	0.3422	ambiguous	-0.851	Destabilizing	0.893	D	0.429	neutral	None	None	None	None	N
F/I	0.2696	likely_benign	0.2172	benign	-1.225	Destabilizing	0.473	N	0.289	neutral	N	0.47987842	None	None	N
F/K	0.6673	likely_pathogenic	0.5755	pathogenic	-0.685	Destabilizing	0.704	D	0.511	neutral	None	None	None	None	N
F/L	0.7407	likely_pathogenic	0.6556	pathogenic	-1.225	Destabilizing	0.27	N	0.243	neutral	N	0.443994978	None	None	N
F/M	0.5223	ambiguous	0.4295	ambiguous	-0.688	Destabilizing	0.944	D	0.378	neutral	None	None	None	None	N
F/N	0.506	ambiguous	0.4148	ambiguous	-0.471	Destabilizing	0.031	N	0.263	neutral	None	None	None	None	N
F/P	0.8789	likely_pathogenic	0.8607	pathogenic	-1.497	Destabilizing	0.944	D	0.51	neutral	None	None	None	None	N
F/Q	0.5879	likely_pathogenic	0.5027	ambiguous	-0.692	Destabilizing	0.944	D	0.521	neutral	None	None	None	None	N
F/R	0.471	ambiguous	0.4064	ambiguous	0.029	Stabilizing	0.944	D	0.524	neutral	None	None	None	None	N
F/S	0.2652	likely_benign	0.2235	benign	-1.203	Destabilizing	0.065	N	0.211	neutral	N	0.443877548	None	None	N
F/T	0.3864	ambiguous	0.2998	benign	-1.099	Destabilizing	0.329	N	0.463	neutral	None	None	None	None	N
F/V	0.2803	likely_benign	0.2196	benign	-1.497	Destabilizing	0.023	N	0.127	neutral	N	0.469200067	None	None	N
F/W	0.3449	ambiguous	0.3208	benign	-0.82	Destabilizing	0.985	D	0.395	neutral	None	None	None	None	N
F/Y	0.114	likely_benign	0.1075	benign	-0.876	Destabilizing	0.006	N	0.121	neutral	N	0.418925962	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.