TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19967	60124;60125;60126	chr2:178592005;178592004;178592003	chr2:179456732;179456731;179456730
N2AB	18326	55201;55202;55203	chr2:178592005;178592004;178592003	chr2:179456732;179456731;179456730
N2A	17399	52420;52421;52422	chr2:178592005;178592004;178592003	chr2:179456732;179456731;179456730
N2B	10902	32929;32930;32931	chr2:178592005;178592004;178592003	chr2:179456732;179456731;179456730
Novex-1	11027	33304;33305;33306	chr2:178592005;178592004;178592003	chr2:179456732;179456731;179456730
Novex-2	11094	33505;33506;33507	chr2:178592005;178592004;178592003	chr2:179456732;179456731;179456730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-32
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.7313
• 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
K/E	rs780485428	-0.091	0.682	N	0.428	0.25	0.241078983079	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/E	rs780485428	-0.091	0.682	N	0.428	0.25	0.241078983079	gnomAD-4.0.0	4.79194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29788E-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
K/A	0.2688	likely_benign	0.2615	benign	0.039	Stabilizing	0.74	D	0.453	neutral	None	None	None	None	N
K/C	0.6472	likely_pathogenic	0.6429	pathogenic	-0.476	Destabilizing	0.996	D	0.707	prob.delet.	None	None	None	None	N
K/D	0.4597	ambiguous	0.4731	ambiguous	-0.367	Destabilizing	0.909	D	0.612	neutral	None	None	None	None	N
K/E	0.1608	likely_benign	0.1592	benign	-0.36	Destabilizing	0.682	D	0.428	neutral	N	0.428163442	None	None	N
K/F	0.6252	likely_pathogenic	0.6289	pathogenic	-0.244	Destabilizing	0.996	D	0.665	prob.neutral	None	None	None	None	N
K/G	0.388	ambiguous	0.3811	ambiguous	-0.112	Destabilizing	0.909	D	0.369	neutral	None	None	None	None	N
K/H	0.2759	likely_benign	0.2721	benign	-0.201	Destabilizing	0.987	D	0.599	neutral	None	None	None	None	N
K/I	0.2727	likely_benign	0.2798	benign	0.361	Stabilizing	0.938	D	0.719	prob.delet.	N	0.497562025	None	None	N
K/L	0.2664	likely_benign	0.2692	benign	0.361	Stabilizing	0.909	D	0.369	neutral	None	None	None	None	N
K/M	0.2075	likely_benign	0.209	benign	-0.158	Destabilizing	0.996	D	0.595	neutral	None	None	None	None	N
K/N	0.32	likely_benign	0.3374	benign	-0.074	Destabilizing	0.883	D	0.63	neutral	N	0.497735383	None	None	N
K/P	0.7798	likely_pathogenic	0.7625	pathogenic	0.278	Stabilizing	0.984	D	0.617	neutral	None	None	None	None	N
K/Q	0.1204	likely_benign	0.1171	benign	-0.172	Destabilizing	0.883	D	0.652	prob.neutral	N	0.454888683	None	None	N
K/R	0.0892	likely_benign	0.0881	benign	-0.119	Destabilizing	0.007	N	0.253	neutral	N	0.479053622	None	None	N
K/S	0.3223	likely_benign	0.3229	benign	-0.383	Destabilizing	0.74	D	0.58	neutral	None	None	None	None	N
K/T	0.1487	likely_benign	0.1483	benign	-0.254	Destabilizing	0.883	D	0.554	neutral	N	0.496175158	None	None	N
K/V	0.2446	likely_benign	0.2392	benign	0.278	Stabilizing	0.953	D	0.628	neutral	None	None	None	None	N
K/W	0.7361	likely_pathogenic	0.7234	pathogenic	-0.376	Destabilizing	0.996	D	0.706	prob.delet.	None	None	None	None	N
K/Y	0.5184	ambiguous	0.5268	ambiguous	-0.024	Destabilizing	0.984	D	0.648	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.