TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21310	64153;64154;64155	chr2:178587283;178587282;178587281	chr2:179452010;179452009;179452008
N2AB	19669	59230;59231;59232	chr2:178587283;178587282;178587281	chr2:179452010;179452009;179452008
N2A	18742	56449;56450;56451	chr2:178587283;178587282;178587281	chr2:179452010;179452009;179452008
N2B	12245	36958;36959;36960	chr2:178587283;178587282;178587281	chr2:179452010;179452009;179452008
Novex-1	12370	37333;37334;37335	chr2:178587283;178587282;178587281	chr2:179452010;179452009;179452008
Novex-2	12437	37534;37535;37536	chr2:178587283;178587282;178587281	chr2:179452010;179452009;179452008
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: Fn3-42
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4431
• 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/K	None	None	0.025	N	0.321	0.133	0.305730143919	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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	0.9244	likely_pathogenic	0.8536	pathogenic	-0.562	Destabilizing	0.845	D	0.449	neutral	None	None	None	None	N
R/C	0.547	ambiguous	0.3638	ambiguous	-0.471	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
R/D	0.98	likely_pathogenic	0.9537	pathogenic	-0.074	Destabilizing	0.975	D	0.489	neutral	None	None	None	None	N
R/E	0.8972	likely_pathogenic	0.8031	pathogenic	0.002	Stabilizing	0.845	D	0.401	neutral	None	None	None	None	N
R/F	0.9402	likely_pathogenic	0.8949	pathogenic	-0.676	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	N
R/G	0.7938	likely_pathogenic	0.6204	pathogenic	-0.806	Destabilizing	0.892	D	0.388	neutral	N	0.484672872	None	None	N
R/H	0.3311	likely_benign	0.2106	benign	-1.177	Destabilizing	0.987	D	0.463	neutral	None	None	None	None	N
R/I	0.8818	likely_pathogenic	0.8037	pathogenic	0.067	Stabilizing	0.983	D	0.593	neutral	N	0.497057136	None	None	N
R/K	0.2658	likely_benign	0.1889	benign	-0.572	Destabilizing	0.025	N	0.321	neutral	N	0.469647492	None	None	N
R/L	0.7639	likely_pathogenic	0.6387	pathogenic	0.067	Stabilizing	0.916	D	0.388	neutral	None	None	None	None	N
R/M	0.7929	likely_pathogenic	0.6743	pathogenic	-0.129	Destabilizing	0.999	D	0.465	neutral	None	None	None	None	N
R/N	0.9551	likely_pathogenic	0.9126	pathogenic	-0.015	Destabilizing	0.975	D	0.431	neutral	None	None	None	None	N
R/P	0.9887	likely_pathogenic	0.9757	pathogenic	-0.122	Destabilizing	0.987	D	0.496	neutral	None	None	None	None	N
R/Q	0.3262	likely_benign	0.2105	benign	-0.266	Destabilizing	0.975	D	0.446	neutral	None	None	None	None	N
R/S	0.9454	likely_pathogenic	0.8854	pathogenic	-0.675	Destabilizing	0.892	D	0.437	neutral	N	0.458179704	None	None	N
R/T	0.8784	likely_pathogenic	0.7717	pathogenic	-0.447	Destabilizing	0.967	D	0.444	neutral	N	0.470898286	None	None	N
R/V	0.9068	likely_pathogenic	0.8368	pathogenic	-0.122	Destabilizing	0.975	D	0.583	neutral	None	None	None	None	N
R/W	0.5899	likely_pathogenic	0.4534	ambiguous	-0.47	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
R/Y	0.8742	likely_pathogenic	0.7842	pathogenic	-0.125	Destabilizing	0.996	D	0.512	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.