TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7467	22624;22625;22626	chr2:178722388;178722387;178722386	chr2:179587115;179587114;179587113
N2AB	7150	21673;21674;21675	chr2:178722388;178722387;178722386	chr2:179587115;179587114;179587113
N2A	6223	18892;18893;18894	chr2:178722388;178722387;178722386	chr2:179587115;179587114;179587113
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-59
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.4357
• Predicted PPI site: I

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
T/I	rs967100948	None	None	N	0.203	0.072	0.19670166235	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs967100948	None	None	N	0.203	0.072	0.19670166235	gnomAD-4.0.0	1.31524E-05	None	None	None	None	I	None	4.82859E-05	0	None	0	0	None	0	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
T/A	0.1044	likely_benign	0.1156	benign	-1.131	Destabilizing	None	N	0.095	neutral	N	0.479801062	None	None	I
T/C	0.5096	ambiguous	0.5011	ambiguous	-0.618	Destabilizing	0.5	N	0.546	neutral	None	None	None	None	I
T/D	0.583	likely_pathogenic	0.6213	pathogenic	-0.415	Destabilizing	0.076	N	0.579	neutral	None	None	None	None	I
T/E	0.4116	ambiguous	0.4297	ambiguous	-0.35	Destabilizing	0.119	N	0.495	neutral	None	None	None	None	I
T/F	0.2857	likely_benign	0.2736	benign	-1.113	Destabilizing	0.335	N	0.59	neutral	None	None	None	None	I
T/G	0.3085	likely_benign	0.3527	ambiguous	-1.454	Destabilizing	0.065	N	0.491	neutral	None	None	None	None	I
T/H	0.3128	likely_benign	0.3178	benign	-1.698	Destabilizing	0.803	D	0.574	neutral	None	None	None	None	I
T/I	0.2109	likely_benign	0.2161	benign	-0.337	Destabilizing	None	N	0.203	neutral	N	0.399894697	None	None	I
T/K	0.2542	likely_benign	0.2527	benign	-0.693	Destabilizing	0.159	N	0.473	neutral	None	None	None	None	I
T/L	0.1108	likely_benign	0.0934	benign	-0.337	Destabilizing	None	N	0.209	neutral	None	None	None	None	I
T/M	0.0818	likely_benign	0.0659	benign	-0.05	Destabilizing	0.001	N	0.237	neutral	None	None	None	None	I
T/N	0.1792	likely_benign	0.1955	benign	-0.846	Destabilizing	0.058	N	0.475	neutral	N	0.490087329	None	None	I
T/P	0.2745	likely_benign	0.3311	benign	-0.569	Destabilizing	0.058	N	0.587	neutral	N	0.496541384	None	None	I
T/Q	0.2603	likely_benign	0.2567	benign	-0.876	Destabilizing	0.236	N	0.607	neutral	None	None	None	None	I
T/R	0.2026	likely_benign	0.2015	benign	-0.618	Destabilizing	0.335	N	0.577	neutral	None	None	None	None	I
T/S	0.1233	likely_benign	0.1477	benign	-1.166	Destabilizing	0.002	N	0.319	neutral	N	0.514876428	None	None	I
T/V	0.1722	likely_benign	0.1656	benign	-0.569	Destabilizing	0.005	N	0.253	neutral	None	None	None	None	I
T/W	0.6006	likely_pathogenic	0.5898	pathogenic	-1.061	Destabilizing	0.976	D	0.575	neutral	None	None	None	None	I
T/Y	0.3012	likely_benign	0.3067	benign	-0.804	Destabilizing	0.782	D	0.651	neutral	None	None	None	None	I

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.