TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22398	67417;67418;67419	chr2:178580095;178580094;178580093	chr2:179444822;179444821;179444820
N2AB	20757	62494;62495;62496	chr2:178580095;178580094;178580093	chr2:179444822;179444821;179444820
N2A	19830	59713;59714;59715	chr2:178580095;178580094;178580093	chr2:179444822;179444821;179444820
N2B	13333	40222;40223;40224	chr2:178580095;178580094;178580093	chr2:179444822;179444821;179444820
Novex-1	13458	40597;40598;40599	chr2:178580095;178580094;178580093	chr2:179444822;179444821;179444820
Novex-2	13525	40798;40799;40800	chr2:178580095;178580094;178580093	chr2:179444822;179444821;179444820
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-50
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2965
• 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
R/K	None	None	0.997	N	0.389	0.257	0.352262096564	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.8308	likely_pathogenic	0.8199	pathogenic	-0.382	Destabilizing	0.999	D	0.417	neutral	None	None	None	None	N
R/C	0.4577	ambiguous	0.4035	ambiguous	-0.294	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
R/D	0.9458	likely_pathogenic	0.945	pathogenic	-0.024	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
R/E	0.7674	likely_pathogenic	0.7537	pathogenic	0.066	Stabilizing	0.999	D	0.473	neutral	None	None	None	None	N
R/F	0.8777	likely_pathogenic	0.875	pathogenic	-0.404	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
R/G	0.5939	likely_pathogenic	0.572	pathogenic	-0.647	Destabilizing	1.0	D	0.536	neutral	N	0.511339399	None	None	N
R/H	0.2622	likely_benign	0.2367	benign	-1.065	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
R/I	0.737	likely_pathogenic	0.7382	pathogenic	0.306	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
R/K	0.1858	likely_benign	0.1681	benign	-0.427	Destabilizing	0.997	D	0.389	neutral	N	0.462105444	None	None	N
R/L	0.6224	likely_pathogenic	0.5887	pathogenic	0.306	Stabilizing	1.0	D	0.536	neutral	None	None	None	None	N
R/M	0.5614	ambiguous	0.5439	ambiguous	0.004	Stabilizing	1.0	D	0.655	neutral	N	0.469077833	None	None	N
R/N	0.8754	likely_pathogenic	0.8712	pathogenic	0.079	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	N
R/P	0.9821	likely_pathogenic	0.9855	pathogenic	0.098	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
R/Q	0.2286	likely_benign	0.1994	benign	-0.107	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
R/S	0.89	likely_pathogenic	0.8786	pathogenic	-0.511	Destabilizing	1.0	D	0.576	neutral	N	0.475149312	None	None	N
R/T	0.7396	likely_pathogenic	0.7176	pathogenic	-0.263	Destabilizing	1.0	D	0.577	neutral	N	0.493793788	None	None	N
R/V	0.8158	likely_pathogenic	0.8024	pathogenic	0.098	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
R/W	0.4405	ambiguous	0.4266	ambiguous	-0.223	Destabilizing	1.0	D	0.743	deleterious	N	0.485295984	None	None	N
R/Y	0.7437	likely_pathogenic	0.7233	pathogenic	0.121	Stabilizing	1.0	D	0.675	prob.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.