TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20887	62884;62885;62886	chr2:178589066;178589065;178589064	chr2:179453793;179453792;179453791
N2AB	19246	57961;57962;57963	chr2:178589066;178589065;178589064	chr2:179453793;179453792;179453791
N2A	18319	55180;55181;55182	chr2:178589066;178589065;178589064	chr2:179453793;179453792;179453791
N2B	11822	35689;35690;35691	chr2:178589066;178589065;178589064	chr2:179453793;179453792;179453791
Novex-1	11947	36064;36065;36066	chr2:178589066;178589065;178589064	chr2:179453793;179453792;179453791
Novex-2	12014	36265;36266;36267	chr2:178589066;178589065;178589064	chr2:179453793;179453792;179453791
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-39
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4575
• 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	0.921	N	0.532	0.356	0.449088463789	gnomAD-4.0.0	1.6025E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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	0.0665	likely_benign	0.0651	benign	-1.984	Destabilizing	0.238	N	0.219	neutral	N	0.484294444	None	None	N
P/C	0.4373	ambiguous	0.4184	ambiguous	-1.388	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
P/D	0.538	ambiguous	0.51	ambiguous	-2.273	Highly Destabilizing	0.939	D	0.48	neutral	None	None	None	None	N
P/E	0.2621	likely_benign	0.2471	benign	-2.141	Highly Destabilizing	0.293	N	0.347	neutral	None	None	None	None	N
P/F	0.397	ambiguous	0.3674	ambiguous	-1.322	Destabilizing	0.995	D	0.617	neutral	None	None	None	None	N
P/G	0.3589	ambiguous	0.3136	benign	-2.431	Highly Destabilizing	0.039	N	0.383	neutral	None	None	None	None	N
P/H	0.2193	likely_benign	0.2028	benign	-1.964	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	N
P/I	0.1477	likely_benign	0.1558	benign	-0.782	Destabilizing	0.489	N	0.437	neutral	None	None	None	None	N
P/K	0.2272	likely_benign	0.2252	benign	-1.799	Destabilizing	0.969	D	0.477	neutral	None	None	None	None	N
P/L	0.0809	likely_benign	0.0815	benign	-0.782	Destabilizing	0.921	D	0.532	neutral	N	0.484733915	None	None	N
P/M	0.1893	likely_benign	0.1908	benign	-0.634	Destabilizing	0.995	D	0.597	neutral	None	None	None	None	N
P/N	0.3578	ambiguous	0.3465	ambiguous	-1.849	Destabilizing	0.995	D	0.621	neutral	None	None	None	None	N
P/Q	0.1485	likely_benign	0.136	benign	-1.853	Destabilizing	0.988	D	0.614	neutral	N	0.478897792	None	None	N
P/R	0.1812	likely_benign	0.1697	benign	-1.376	Destabilizing	0.988	D	0.618	neutral	D	0.525066418	None	None	N
P/S	0.1334	likely_benign	0.1246	benign	-2.416	Highly Destabilizing	0.921	D	0.492	neutral	N	0.487518619	None	None	N
P/T	0.0983	likely_benign	0.098	benign	-2.153	Highly Destabilizing	0.959	D	0.476	neutral	N	0.487772108	None	None	N
P/V	0.1141	likely_benign	0.1162	benign	-1.152	Destabilizing	0.864	D	0.489	neutral	None	None	None	None	N
P/W	0.7018	likely_pathogenic	0.6551	pathogenic	-1.679	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
P/Y	0.4439	ambiguous	0.421	ambiguous	-1.347	Destabilizing	0.999	D	0.616	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.