TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30064	90415;90416;90417	chr2:178552710;178552709;178552708	chr2:179417437;179417436;179417435
N2AB	28423	85492;85493;85494	chr2:178552710;178552709;178552708	chr2:179417437;179417436;179417435
N2A	27496	82711;82712;82713	chr2:178552710;178552709;178552708	chr2:179417437;179417436;179417435
N2B	20999	63220;63221;63222	chr2:178552710;178552709;178552708	chr2:179417437;179417436;179417435
Novex-1	21124	63595;63596;63597	chr2:178552710;178552709;178552708	chr2:179417437;179417436;179417435
Novex-2	21191	63796;63797;63798	chr2:178552710;178552709;178552708	chr2:179417437;179417436;179417435
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-107
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.2767
• 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
E/Q	rs866186866	-0.807	0.22	N	0.528	0.213	0.239305524855	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
E/Q	rs866186866	-0.807	0.22	N	0.528	0.213	0.239305524855	gnomAD-4.0.0	1.59103E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88246E-05	0	0	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
E/A	0.1577	likely_benign	0.1427	benign	-0.858	Destabilizing	0.22	N	0.612	neutral	N	0.452621956	None	None	N
E/C	0.7932	likely_pathogenic	0.7723	pathogenic	-0.428	Destabilizing	0.968	D	0.799	deleterious	None	None	None	None	N
E/D	0.0628	likely_benign	0.0665	benign	-0.995	Destabilizing	None	N	0.144	neutral	N	0.430977247	None	None	N
E/F	0.8425	likely_pathogenic	0.8051	pathogenic	-0.059	Destabilizing	0.89	D	0.798	deleterious	None	None	None	None	N
E/G	0.1184	likely_benign	0.1154	benign	-1.268	Destabilizing	0.22	N	0.673	neutral	N	0.318032957	None	None	N
E/H	0.4113	ambiguous	0.3802	ambiguous	-0.331	Destabilizing	0.726	D	0.507	neutral	None	None	None	None	N
E/I	0.7123	likely_pathogenic	0.6495	pathogenic	0.275	Stabilizing	0.726	D	0.799	deleterious	None	None	None	None	N
E/K	0.3395	likely_benign	0.294	benign	-0.494	Destabilizing	0.22	N	0.515	neutral	N	0.445039836	None	None	N
E/L	0.6575	likely_pathogenic	0.6006	pathogenic	0.275	Stabilizing	0.567	D	0.764	deleterious	None	None	None	None	N
E/M	0.6556	likely_pathogenic	0.6076	pathogenic	0.725	Stabilizing	0.968	D	0.745	deleterious	None	None	None	None	N
E/N	0.1518	likely_benign	0.1513	benign	-1.082	Destabilizing	0.157	N	0.509	neutral	None	None	None	None	N
E/P	0.97	likely_pathogenic	0.9621	pathogenic	-0.081	Destabilizing	0.726	D	0.689	prob.neutral	None	None	None	None	N
E/Q	0.1814	likely_benign	0.1636	benign	-0.905	Destabilizing	0.22	N	0.528	neutral	N	0.469764922	None	None	N
E/R	0.4645	ambiguous	0.4203	ambiguous	-0.223	Destabilizing	0.567	D	0.518	neutral	None	None	None	None	N
E/S	0.122	likely_benign	0.1221	benign	-1.46	Destabilizing	0.157	N	0.508	neutral	None	None	None	None	N
E/T	0.3092	likely_benign	0.2699	benign	-1.103	Destabilizing	0.272	N	0.649	neutral	None	None	None	None	N
E/V	0.5012	ambiguous	0.4382	ambiguous	-0.081	Destabilizing	0.667	D	0.687	prob.neutral	N	0.466431261	None	None	N
E/W	0.9291	likely_pathogenic	0.9103	pathogenic	0.265	Stabilizing	0.968	D	0.754	deleterious	None	None	None	None	N
E/Y	0.6286	likely_pathogenic	0.5851	pathogenic	0.237	Stabilizing	0.89	D	0.762	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.