TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17091	51496;51497;51498	chr2:178610255;178610254;178610253	chr2:179474982;179474981;179474980
N2AB	15450	46573;46574;46575	chr2:178610255;178610254;178610253	chr2:179474982;179474981;179474980
N2A	14523	43792;43793;43794	chr2:178610255;178610254;178610253	chr2:179474982;179474981;179474980
N2B	8026	24301;24302;24303	chr2:178610255;178610254;178610253	chr2:179474982;179474981;179474980
Novex-1	8151	24676;24677;24678	chr2:178610255;178610254;178610253	chr2:179474982;179474981;179474980
Novex-2	8218	24877;24878;24879	chr2:178610255;178610254;178610253	chr2:179474982;179474981;179474980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-12
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3265
• 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
R/T	None	None	1.0	N	0.573	0.438	0.370789594751	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
R/A	0.9807	likely_pathogenic	0.9682	pathogenic	-0.264	Destabilizing	0.999	D	0.441	neutral	None	None	None	None	N
R/C	0.8778	likely_pathogenic	0.788	pathogenic	-0.32	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
R/D	0.9926	likely_pathogenic	0.988	pathogenic	0.019	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	N
R/E	0.9591	likely_pathogenic	0.936	pathogenic	0.09	Stabilizing	0.999	D	0.48	neutral	None	None	None	None	N
R/F	0.9806	likely_pathogenic	0.9696	pathogenic	-0.416	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
R/G	0.9519	likely_pathogenic	0.9159	pathogenic	-0.485	Destabilizing	1.0	D	0.522	neutral	N	0.483595437	None	None	N
R/H	0.6857	likely_pathogenic	0.553	ambiguous	-0.857	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
R/I	0.958	likely_pathogenic	0.9356	pathogenic	0.293	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
R/K	0.4836	ambiguous	0.4003	ambiguous	-0.268	Destabilizing	0.997	D	0.394	neutral	N	0.471533004	None	None	N
R/L	0.8985	likely_pathogenic	0.8469	pathogenic	0.293	Stabilizing	1.0	D	0.522	neutral	None	None	None	None	N
R/M	0.9438	likely_pathogenic	0.9139	pathogenic	-0.037	Destabilizing	1.0	D	0.649	neutral	N	0.474673694	None	None	N
R/N	0.9818	likely_pathogenic	0.9711	pathogenic	0.112	Stabilizing	1.0	D	0.613	neutral	None	None	None	None	N
R/P	0.9937	likely_pathogenic	0.9904	pathogenic	0.128	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	N
R/Q	0.6461	likely_pathogenic	0.5157	ambiguous	-0.067	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
R/S	0.985	likely_pathogenic	0.9735	pathogenic	-0.427	Destabilizing	1.0	D	0.572	neutral	N	0.45925714	None	None	N
R/T	0.9668	likely_pathogenic	0.9407	pathogenic	-0.21	Destabilizing	1.0	D	0.573	neutral	N	0.475208027	None	None	N
R/V	0.9675	likely_pathogenic	0.9505	pathogenic	0.128	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
R/W	0.8535	likely_pathogenic	0.7613	pathogenic	-0.327	Destabilizing	1.0	D	0.733	prob.delet.	N	0.473116758	None	None	N
R/Y	0.9579	likely_pathogenic	0.9338	pathogenic	0.052	Stabilizing	1.0	D	0.654	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.