TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19618	59077;59078;59079	chr2:178593356;178593355;178593354	chr2:179458083;179458082;179458081
N2AB	17977	54154;54155;54156	chr2:178593356;178593355;178593354	chr2:179458083;179458082;179458081
N2A	17050	51373;51374;51375	chr2:178593356;178593355;178593354	chr2:179458083;179458082;179458081
N2B	10553	31882;31883;31884	chr2:178593356;178593355;178593354	chr2:179458083;179458082;179458081
Novex-1	10678	32257;32258;32259	chr2:178593356;178593355;178593354	chr2:179458083;179458082;179458081
Novex-2	10745	32458;32459;32460	chr2:178593356;178593355;178593354	chr2:179458083;179458082;179458081
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-30
• Domain position: 40
• Structural Position: 43
• Q(SASA): 0.1329
• 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	None	N	0.143	0.125	0.243398259712	gnomAD-4.0.0	1.36874E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79923E-06	0	0
R/T	None	None	0.324	N	0.513	0.338	0.314716216878	gnomAD-4.0.0	1.36874E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79923E-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	0.945	likely_pathogenic	0.9513	pathogenic	-2.104	Highly Destabilizing	0.116	N	0.414	neutral	None	None	None	None	N
R/C	0.5636	ambiguous	0.5669	pathogenic	-2.002	Highly Destabilizing	0.981	D	0.603	neutral	None	None	None	None	N
R/D	0.993	likely_pathogenic	0.9938	pathogenic	-1.075	Destabilizing	0.388	N	0.547	neutral	None	None	None	None	N
R/E	0.9205	likely_pathogenic	0.9271	pathogenic	-0.864	Destabilizing	0.116	N	0.431	neutral	None	None	None	None	N
R/F	0.9663	likely_pathogenic	0.9714	pathogenic	-1.381	Destabilizing	0.932	D	0.623	neutral	None	None	None	None	N
R/G	0.918	likely_pathogenic	0.9205	pathogenic	-2.428	Highly Destabilizing	0.324	N	0.541	neutral	N	0.483462786	None	None	N
R/H	0.418	ambiguous	0.4218	ambiguous	-2.305	Highly Destabilizing	0.818	D	0.529	neutral	None	None	None	None	N
R/I	0.9109	likely_pathogenic	0.9149	pathogenic	-1.16	Destabilizing	0.773	D	0.629	neutral	N	0.503782314	None	None	N
R/K	0.1399	likely_benign	0.1398	benign	-1.364	Destabilizing	None	N	0.143	neutral	N	0.388783908	None	None	N
R/L	0.8322	likely_pathogenic	0.8451	pathogenic	-1.16	Destabilizing	0.388	N	0.541	neutral	None	None	None	None	N
R/M	0.8194	likely_pathogenic	0.8254	pathogenic	-1.652	Destabilizing	0.932	D	0.541	neutral	None	None	None	None	N
R/N	0.9749	likely_pathogenic	0.9769	pathogenic	-1.33	Destabilizing	0.388	N	0.492	neutral	None	None	None	None	N
R/P	0.9976	likely_pathogenic	0.9975	pathogenic	-1.465	Destabilizing	0.563	D	0.606	neutral	None	None	None	None	N
R/Q	0.3774	ambiguous	0.3809	ambiguous	-1.207	Destabilizing	0.241	N	0.494	neutral	None	None	None	None	N
R/S	0.9795	likely_pathogenic	0.981	pathogenic	-2.228	Highly Destabilizing	0.09	N	0.485	neutral	N	0.51465185	None	None	N
R/T	0.9424	likely_pathogenic	0.948	pathogenic	-1.811	Destabilizing	0.324	N	0.513	neutral	N	0.496945459	None	None	N
R/V	0.9249	likely_pathogenic	0.93	pathogenic	-1.465	Destabilizing	0.388	N	0.579	neutral	None	None	None	None	N
R/W	0.7845	likely_pathogenic	0.7774	pathogenic	-0.923	Destabilizing	0.981	D	0.635	neutral	None	None	None	None	N
R/Y	0.9073	likely_pathogenic	0.9141	pathogenic	-0.778	Destabilizing	0.932	D	0.604	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.