TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17424	52495;52496;52497	chr2:178608741;178608740;178608739	chr2:179473468;179473467;179473466
N2AB	15783	47572;47573;47574	chr2:178608741;178608740;178608739	chr2:179473468;179473467;179473466
N2A	14856	44791;44792;44793	chr2:178608741;178608740;178608739	chr2:179473468;179473467;179473466
N2B	8359	25300;25301;25302	chr2:178608741;178608740;178608739	chr2:179473468;179473467;179473466
Novex-1	8484	25675;25676;25677	chr2:178608741;178608740;178608739	chr2:179473468;179473467;179473466
Novex-2	8551	25876;25877;25878	chr2:178608741;178608740;178608739	chr2:179473468;179473467;179473466
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-14
• Domain position: 56
• Structural Position: 75
• Q(SASA): 0.5878
• 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	rs1559751874	None	0.204	N	0.248	0.259	0.359151904892	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/I	rs1559751874	None	0.204	N	0.248	0.259	0.359151904892	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1559751874	None	0.204	N	0.248	0.259	0.359151904892	gnomAD-4.0.0	2.48061E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54402E-06	1.09823E-05	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	0.1821	likely_benign	0.1579	benign	-0.454	Destabilizing	0.63	D	0.381	neutral	N	0.509283315	None	None	I
T/C	0.7604	likely_pathogenic	0.7096	pathogenic	-0.186	Destabilizing	0.999	D	0.423	neutral	None	None	None	None	I
T/D	0.8126	likely_pathogenic	0.8129	pathogenic	0.142	Stabilizing	0.975	D	0.371	neutral	None	None	None	None	I
T/E	0.8032	likely_pathogenic	0.7974	pathogenic	0.057	Stabilizing	0.975	D	0.367	neutral	None	None	None	None	I
T/F	0.6796	likely_pathogenic	0.6257	pathogenic	-1.024	Destabilizing	0.987	D	0.489	neutral	None	None	None	None	I
T/G	0.434	ambiguous	0.4254	ambiguous	-0.563	Destabilizing	0.845	D	0.4	neutral	None	None	None	None	I
T/H	0.6408	likely_pathogenic	0.6073	pathogenic	-0.938	Destabilizing	0.999	D	0.484	neutral	None	None	None	None	I
T/I	0.6083	likely_pathogenic	0.5291	ambiguous	-0.284	Destabilizing	0.204	N	0.248	neutral	N	0.509323388	None	None	I
T/K	0.6849	likely_pathogenic	0.6899	pathogenic	-0.271	Destabilizing	0.967	D	0.371	neutral	N	0.505626935	None	None	I
T/L	0.3248	likely_benign	0.2804	benign	-0.284	Destabilizing	0.845	D	0.405	neutral	None	None	None	None	I
T/M	0.2453	likely_benign	0.2034	benign	0.062	Stabilizing	0.997	D	0.396	neutral	None	None	None	None	I
T/N	0.3301	likely_benign	0.3084	benign	-0.024	Destabilizing	0.975	D	0.359	neutral	None	None	None	None	I
T/P	0.4209	ambiguous	0.3803	ambiguous	-0.314	Destabilizing	0.983	D	0.395	neutral	N	0.487211745	None	None	I
T/Q	0.5901	likely_pathogenic	0.5615	ambiguous	-0.31	Destabilizing	0.975	D	0.389	neutral	None	None	None	None	I
T/R	0.6371	likely_pathogenic	0.6366	pathogenic	-0.003	Destabilizing	0.967	D	0.39	neutral	N	0.509976749	None	None	I
T/S	0.2217	likely_benign	0.2126	benign	-0.248	Destabilizing	0.099	N	0.293	neutral	N	0.49211892	None	None	I
T/V	0.4188	ambiguous	0.3601	ambiguous	-0.314	Destabilizing	0.845	D	0.369	neutral	None	None	None	None	I
T/W	0.9243	likely_pathogenic	0.9094	pathogenic	-0.997	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	I
T/Y	0.7241	likely_pathogenic	0.6918	pathogenic	-0.713	Destabilizing	0.996	D	0.499	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.