TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10141	30646;30647;30648	chr2:178702466;178702465;178702464	chr2:179567193;179567192;179567191
N2AB	9824	29695;29696;29697	chr2:178702466;178702465;178702464	chr2:179567193;179567192;179567191
N2A	8897	26914;26915;26916	chr2:178702466;178702465;178702464	chr2:179567193;179567192;179567191
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-86
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.3139
• 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/A	None	None	0.001	None	0.123	0.097	0.0884992946249	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
P/A	0.1433	likely_benign	0.1268	benign	-0.585	Destabilizing	0.001	N	0.123	neutral	None	None	None	None	N
P/C	0.9386	likely_pathogenic	0.9432	pathogenic	-0.461	Destabilizing	0.951	D	0.41	neutral	None	None	None	None	N
P/D	0.8914	likely_pathogenic	0.8815	pathogenic	-0.64	Destabilizing	0.418	N	0.319	neutral	None	None	None	None	N
P/E	0.6378	likely_pathogenic	0.6093	pathogenic	-0.757	Destabilizing	0.418	N	0.347	neutral	None	None	None	None	N
P/F	0.9416	likely_pathogenic	0.9413	pathogenic	-0.836	Destabilizing	0.836	D	0.446	neutral	None	None	None	None	N
P/G	0.7726	likely_pathogenic	0.7345	pathogenic	-0.736	Destabilizing	0.129	N	0.309	neutral	None	None	None	None	N
P/H	0.625	likely_pathogenic	0.6124	pathogenic	-0.369	Destabilizing	0.836	D	0.383	neutral	None	None	None	None	N
P/I	0.7751	likely_pathogenic	0.7873	pathogenic	-0.332	Destabilizing	0.004	N	0.219	neutral	None	None	None	None	N
P/K	0.646	likely_pathogenic	0.6052	pathogenic	-0.558	Destabilizing	0.264	N	0.343	neutral	None	None	None	None	N
P/L	0.3819	ambiguous	0.4041	ambiguous	-0.332	Destabilizing	0.101	N	0.334	neutral	None	None	None	None	N
P/M	0.7679	likely_pathogenic	0.7576	pathogenic	-0.267	Destabilizing	0.836	D	0.401	neutral	None	None	None	None	N
P/N	0.8683	likely_pathogenic	0.8446	pathogenic	-0.179	Destabilizing	0.264	N	0.41	neutral	None	None	None	None	N
P/Q	0.4482	ambiguous	0.4212	ambiguous	-0.462	Destabilizing	0.655	D	0.364	neutral	None	None	None	None	N
P/R	0.4408	ambiguous	0.4124	ambiguous	0.014	Stabilizing	0.655	D	0.452	neutral	None	None	None	None	N
P/S	0.3947	ambiguous	0.3558	ambiguous	-0.492	Destabilizing	0.003	N	0.127	neutral	None	None	None	None	N
P/T	0.3664	ambiguous	0.3461	ambiguous	-0.515	Destabilizing	0.007	N	0.17	neutral	None	None	None	None	N
P/V	0.5821	likely_pathogenic	0.5655	pathogenic	-0.382	Destabilizing	0.129	N	0.299	neutral	None	None	None	None	N
P/W	0.9673	likely_pathogenic	0.9683	pathogenic	-0.932	Destabilizing	0.983	D	0.449	neutral	None	None	None	None	N
P/Y	0.9207	likely_pathogenic	0.9227	pathogenic	-0.633	Destabilizing	0.94	D	0.449	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.