TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29791	89596;89597;89598	chr2:178553634;178553633;178553632	chr2:179418361;179418360;179418359
N2AB	28150	84673;84674;84675	chr2:178553634;178553633;178553632	chr2:179418361;179418360;179418359
N2A	27223	81892;81893;81894	chr2:178553634;178553633;178553632	chr2:179418361;179418360;179418359
N2B	20726	62401;62402;62403	chr2:178553634;178553633;178553632	chr2:179418361;179418360;179418359
Novex-1	20851	62776;62777;62778	chr2:178553634;178553633;178553632	chr2:179418361;179418360;179418359
Novex-2	20918	62977;62978;62979	chr2:178553634;178553633;178553632	chr2:179418361;179418360;179418359
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: Fn3-105
• Domain position: 58
• Structural Position: 83
• Q(SASA): 0.8003
• Predicted PPI site: I

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/S	None	None	0.98	N	0.589	0.291	0.253205268125	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/T	rs1360436599	-0.062	0.99	N	0.582	0.376	0.418095516054	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/T	rs1360436599	-0.062	0.99	N	0.582	0.376	0.418095516054	gnomAD-4.0.0	3.18227E-06	None	None	None	None	I	None	0	4.57247E-05	None	0	0	None	0	0	0	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	0.439	ambiguous	0.3893	ambiguous	-0.093	Destabilizing	0.985	D	0.566	neutral	None	None	None	None	I
R/C	0.2116	likely_benign	0.1712	benign	-0.321	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
R/D	0.7037	likely_pathogenic	0.651	pathogenic	-0.117	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	I
R/E	0.4278	ambiguous	0.383	ambiguous	-0.071	Destabilizing	0.985	D	0.56	neutral	None	None	None	None	I
R/F	0.5758	likely_pathogenic	0.5137	ambiguous	-0.387	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
R/G	0.3052	likely_benign	0.262	benign	-0.253	Destabilizing	0.99	D	0.562	neutral	N	0.466567114	None	None	I
R/H	0.1326	likely_benign	0.1158	benign	-0.636	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
R/I	0.2984	likely_benign	0.2479	benign	0.283	Stabilizing	0.999	D	0.664	neutral	N	0.497004665	None	None	I
R/K	0.1079	likely_benign	0.1037	benign	-0.187	Destabilizing	0.219	N	0.248	neutral	N	0.420256035	None	None	I
R/L	0.2665	likely_benign	0.2337	benign	0.283	Stabilizing	0.993	D	0.562	neutral	None	None	None	None	I
R/M	0.2956	likely_benign	0.2586	benign	-0.078	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
R/N	0.5961	likely_pathogenic	0.5341	ambiguous	-0.01	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	I
R/P	0.4789	ambiguous	0.471	ambiguous	0.176	Stabilizing	0.999	D	0.656	neutral	None	None	None	None	I
R/Q	0.1209	likely_benign	0.1077	benign	-0.118	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	I
R/S	0.5562	ambiguous	0.4934	ambiguous	-0.357	Destabilizing	0.98	D	0.589	neutral	N	0.446055769	None	None	I
R/T	0.2839	likely_benign	0.2488	benign	-0.192	Destabilizing	0.99	D	0.582	neutral	N	0.448941359	None	None	I
R/V	0.3754	ambiguous	0.3262	benign	0.176	Stabilizing	0.998	D	0.649	neutral	None	None	None	None	I
R/W	0.22	likely_benign	0.1866	benign	-0.464	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
R/Y	0.4459	ambiguous	0.384	ambiguous	-0.059	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I

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.