TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7599	23020;23021;23022	chr2:178721868;178721867;178721866	chr2:179586595;179586594;179586593
N2AB	7282	22069;22070;22071	chr2:178721868;178721867;178721866	chr2:179586595;179586594;179586593
N2A	6355	19288;19289;19290	chr2:178721868;178721867;178721866	chr2:179586595;179586594;179586593
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-60
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3224
• 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
S/L	None	None	0.997	N	0.651	0.445	0.72449871023	gnomAD-4.0.0	1.59696E-06	None	None	None	None	N	None	0	2.29179E-05	None	0	0	None	0	0	0	0	0
S/P	None	None	1.0	N	0.685	0.531	0.525561869914	gnomAD-4.0.0	1.5965E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	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
S/A	0.0884	likely_benign	0.0857	benign	-0.544	Destabilizing	0.744	D	0.483	neutral	N	0.489442219	None	None	N
S/C	0.1918	likely_benign	0.1757	benign	-0.285	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
S/D	0.4999	ambiguous	0.4826	ambiguous	-0.458	Destabilizing	0.996	D	0.551	neutral	None	None	None	None	N
S/E	0.5601	ambiguous	0.5397	ambiguous	-0.491	Destabilizing	0.997	D	0.553	neutral	None	None	None	None	N
S/F	0.15	likely_benign	0.1446	benign	-0.791	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
S/G	0.1294	likely_benign	0.1316	benign	-0.771	Destabilizing	0.998	D	0.54	neutral	None	None	None	None	N
S/H	0.3445	ambiguous	0.3472	ambiguous	-1.335	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
S/I	0.1452	likely_benign	0.1388	benign	-0.057	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
S/K	0.6427	likely_pathogenic	0.6335	pathogenic	-0.819	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
S/L	0.0922	likely_benign	0.0873	benign	-0.057	Destabilizing	0.997	D	0.651	neutral	N	0.512283416	None	None	N
S/M	0.1938	likely_benign	0.1868	benign	0.318	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
S/N	0.1574	likely_benign	0.1588	benign	-0.643	Destabilizing	0.968	D	0.56	neutral	None	None	None	None	N
S/P	0.5015	ambiguous	0.4867	ambiguous	-0.186	Destabilizing	1.0	D	0.685	prob.neutral	N	0.512536905	None	None	N
S/Q	0.4844	ambiguous	0.4939	ambiguous	-0.842	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
S/R	0.5102	ambiguous	0.5143	ambiguous	-0.643	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
S/T	0.0757	likely_benign	0.0735	benign	-0.629	Destabilizing	0.059	N	0.295	neutral	N	0.49090349	None	None	N
S/V	0.1529	likely_benign	0.145	benign	-0.186	Destabilizing	0.994	D	0.675	prob.neutral	None	None	None	None	N
S/W	0.3323	likely_benign	0.3179	benign	-0.807	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
S/Y	0.1862	likely_benign	0.1745	benign	-0.554	Destabilizing	1.0	D	0.769	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.