TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23155	69688;69689;69690	chr2:178576781;178576780;178576779	chr2:179441508;179441507;179441506
N2AB	21514	64765;64766;64767	chr2:178576781;178576780;178576779	chr2:179441508;179441507;179441506
N2A	20587	61984;61985;61986	chr2:178576781;178576780;178576779	chr2:179441508;179441507;179441506
N2B	14090	42493;42494;42495	chr2:178576781;178576780;178576779	chr2:179441508;179441507;179441506
Novex-1	14215	42868;42869;42870	chr2:178576781;178576780;178576779	chr2:179441508;179441507;179441506
Novex-2	14282	43069;43070;43071	chr2:178576781;178576780;178576779	chr2:179441508;179441507;179441506
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: Fn3-56
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1164
• 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
T/I	None	None	0.317	N	0.652	0.161	0.288352970974	gnomAD-4.0.0	6.84347E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99588E-07	0	0
T/S	rs761306433	-1.385	None	N	0.194	0.054	0.104622674875	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
T/S	rs761306433	-1.385	None	N	0.194	0.054	0.104622674875	gnomAD-4.0.0	1.71087E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.24897E-05	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	0.0809	likely_benign	0.0836	benign	-0.717	Destabilizing	None	N	0.143	neutral	N	0.431652038	None	None	N
T/C	0.3347	likely_benign	0.3151	benign	-0.749	Destabilizing	0.824	D	0.615	neutral	None	None	None	None	N
T/D	0.6334	likely_pathogenic	0.6255	pathogenic	-1.577	Destabilizing	0.081	N	0.607	neutral	None	None	None	None	N
T/E	0.5256	ambiguous	0.5194	ambiguous	-1.519	Destabilizing	0.081	N	0.589	neutral	None	None	None	None	N
T/F	0.2192	likely_benign	0.2098	benign	-0.746	Destabilizing	0.555	D	0.663	neutral	None	None	None	None	N
T/G	0.2132	likely_benign	0.2011	benign	-1.013	Destabilizing	0.035	N	0.548	neutral	None	None	None	None	N
T/H	0.2757	likely_benign	0.2636	benign	-1.354	Destabilizing	0.824	D	0.613	neutral	None	None	None	None	N
T/I	0.3115	likely_benign	0.3286	benign	-0.004	Destabilizing	0.317	N	0.652	neutral	N	0.473018307	None	None	N
T/K	0.4742	ambiguous	0.4741	ambiguous	-0.859	Destabilizing	0.081	N	0.597	neutral	None	None	None	None	N
T/L	0.1453	likely_benign	0.1534	benign	-0.004	Destabilizing	0.149	N	0.552	neutral	None	None	None	None	N
T/M	0.0841	likely_benign	0.0853	benign	0.289	Stabilizing	0.791	D	0.625	neutral	None	None	None	None	N
T/N	0.1694	likely_benign	0.1736	benign	-1.205	Destabilizing	0.062	N	0.579	neutral	N	0.464321817	None	None	N
T/P	0.9228	likely_pathogenic	0.9307	pathogenic	-0.209	Destabilizing	0.317	N	0.665	neutral	N	0.490957978	None	None	N
T/Q	0.3256	likely_benign	0.3285	benign	-1.353	Destabilizing	0.38	N	0.666	neutral	None	None	None	None	N
T/R	0.3854	ambiguous	0.3889	ambiguous	-0.652	Destabilizing	0.38	N	0.668	neutral	None	None	None	None	N
T/S	0.0833	likely_benign	0.077	benign	-1.281	Destabilizing	None	N	0.194	neutral	N	0.343736691	None	None	N
T/V	0.2119	likely_benign	0.2211	benign	-0.209	Destabilizing	0.081	N	0.515	neutral	None	None	None	None	N
T/W	0.6137	likely_pathogenic	0.6126	pathogenic	-0.826	Destabilizing	0.935	D	0.64	neutral	None	None	None	None	N
T/Y	0.2674	likely_benign	0.2699	benign	-0.489	Destabilizing	0.555	D	0.635	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.