TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14006	42241;42242;42243	chr2:178635173;178635172;178635171	chr2:179499900;179499899;179499898
N2AB	12365	37318;37319;37320	chr2:178635173;178635172;178635171	chr2:179499900;179499899;179499898
N2A	11438	34537;34538;34539	chr2:178635173;178635172;178635171	chr2:179499900;179499899;179499898
N2B	4941	15046;15047;15048	chr2:178635173;178635172;178635171	chr2:179499900;179499899;179499898
Novex-1	5066	15421;15422;15423	chr2:178635173;178635172;178635171	chr2:179499900;179499899;179499898
Novex-2	5133	15622;15623;15624	chr2:178635173;178635172;178635171	chr2:179499900;179499899;179499898
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-90
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.577
• 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
P/L	None	None	0.919	N	0.62	0.212	0.299086750705	gnomAD-4.0.0	3.60099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93752E-06	0	0
P/S	None	None	0.919	N	0.412	0.196	0.204665344411	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
P/A	0.3214	likely_benign	0.1607	benign	-0.397	Destabilizing	0.824	D	0.431	neutral	N	0.43630534	None	None	N
P/C	0.9663	likely_pathogenic	0.9137	pathogenic	-0.581	Destabilizing	0.999	D	0.728	deleterious	None	None	None	None	N
P/D	0.8802	likely_pathogenic	0.7424	pathogenic	-0.434	Destabilizing	0.938	D	0.482	neutral	None	None	None	None	N
P/E	0.7336	likely_pathogenic	0.5494	ambiguous	-0.555	Destabilizing	0.883	D	0.413	neutral	None	None	None	None	N
P/F	0.9665	likely_pathogenic	0.8913	pathogenic	-0.712	Destabilizing	0.997	D	0.699	prob.delet.	None	None	None	None	N
P/G	0.846	likely_pathogenic	0.6337	pathogenic	-0.505	Destabilizing	0.968	D	0.527	neutral	None	None	None	None	N
P/H	0.7764	likely_pathogenic	0.54	ambiguous	-0.138	Destabilizing	0.988	D	0.634	neutral	N	0.45416098	None	None	N
P/I	0.903	likely_pathogenic	0.7557	pathogenic	-0.261	Destabilizing	0.997	D	0.716	prob.delet.	None	None	None	None	N
P/K	0.8804	likely_pathogenic	0.7364	pathogenic	-0.439	Destabilizing	0.757	D	0.429	neutral	None	None	None	None	N
P/L	0.656	likely_pathogenic	0.4023	ambiguous	-0.261	Destabilizing	0.919	D	0.62	neutral	N	0.449870206	None	None	N
P/M	0.8974	likely_pathogenic	0.7292	pathogenic	-0.372	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
P/N	0.835	likely_pathogenic	0.6127	pathogenic	-0.148	Destabilizing	0.991	D	0.53	neutral	None	None	None	None	N
P/Q	0.6396	likely_pathogenic	0.3818	ambiguous	-0.4	Destabilizing	0.576	D	0.287	neutral	None	None	None	None	N
P/R	0.7457	likely_pathogenic	0.5402	ambiguous	0.074	Stabilizing	0.034	N	0.552	neutral	N	0.431450516	None	None	N
P/S	0.6076	likely_pathogenic	0.3098	benign	-0.448	Destabilizing	0.919	D	0.412	neutral	N	0.435009496	None	None	N
P/T	0.6506	likely_pathogenic	0.3535	ambiguous	-0.474	Destabilizing	0.958	D	0.51	neutral	N	0.437047554	None	None	N
P/V	0.7882	likely_pathogenic	0.5643	pathogenic	-0.273	Destabilizing	0.991	D	0.547	neutral	None	None	None	None	N
P/W	0.9845	likely_pathogenic	0.9503	pathogenic	-0.799	Destabilizing	0.999	D	0.706	prob.delet.	None	None	None	None	N
P/Y	0.9422	likely_pathogenic	0.8341	pathogenic	-0.5	Destabilizing	0.997	D	0.727	deleterious	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.