TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30290	91093;91094;91095	chr2:178552032;178552031;178552030	chr2:179416759;179416758;179416757
N2AB	28649	86170;86171;86172	chr2:178552032;178552031;178552030	chr2:179416759;179416758;179416757
N2A	27722	83389;83390;83391	chr2:178552032;178552031;178552030	chr2:179416759;179416758;179416757
N2B	21225	63898;63899;63900	chr2:178552032;178552031;178552030	chr2:179416759;179416758;179416757
Novex-1	21350	64273;64274;64275	chr2:178552032;178552031;178552030	chr2:179416759;179416758;179416757
Novex-2	21417	64474;64475;64476	chr2:178552032;178552031;178552030	chr2:179416759;179416758;179416757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-108
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.4714
• 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
V/G	None	None	0.967	N	0.602	0.5	0.827830861967	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85977E-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
V/A	0.2706	likely_benign	0.2159	benign	-0.998	Destabilizing	0.892	D	0.385	neutral	N	0.497084809	None	None	N
V/C	0.7286	likely_pathogenic	0.6706	pathogenic	-0.639	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
V/D	0.6102	likely_pathogenic	0.4837	ambiguous	-0.65	Destabilizing	0.935	D	0.719	prob.delet.	N	0.50820588	None	None	N
V/E	0.4306	ambiguous	0.3294	benign	-0.698	Destabilizing	0.975	D	0.615	neutral	None	None	None	None	N
V/F	0.2569	likely_benign	0.2004	benign	-0.895	Destabilizing	0.967	D	0.585	neutral	N	0.50924603	None	None	N
V/G	0.3006	likely_benign	0.2564	benign	-1.238	Destabilizing	0.967	D	0.602	neutral	N	0.493916811	None	None	N
V/H	0.605	likely_pathogenic	0.4979	ambiguous	-0.677	Destabilizing	0.997	D	0.699	prob.neutral	None	None	None	None	N
V/I	0.0814	likely_benign	0.0744	benign	-0.472	Destabilizing	0.025	N	0.269	neutral	N	0.408351104	None	None	N
V/K	0.4608	ambiguous	0.3338	benign	-0.77	Destabilizing	0.975	D	0.641	neutral	None	None	None	None	N
V/L	0.1715	likely_benign	0.1392	benign	-0.472	Destabilizing	0.369	N	0.437	neutral	N	0.472495796	None	None	N
V/M	0.1629	likely_benign	0.1361	benign	-0.409	Destabilizing	0.975	D	0.519	neutral	None	None	None	None	N
V/N	0.3283	likely_benign	0.2551	benign	-0.512	Destabilizing	0.253	N	0.409	neutral	None	None	None	None	N
V/P	0.8429	likely_pathogenic	0.7659	pathogenic	-0.612	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
V/Q	0.3179	likely_benign	0.2485	benign	-0.708	Destabilizing	0.987	D	0.668	neutral	None	None	None	None	N
V/R	0.4322	ambiguous	0.3102	benign	-0.228	Destabilizing	0.987	D	0.716	prob.delet.	None	None	None	None	N
V/S	0.2807	likely_benign	0.2287	benign	-0.965	Destabilizing	0.975	D	0.537	neutral	None	None	None	None	N
V/T	0.2317	likely_benign	0.1817	benign	-0.903	Destabilizing	0.916	D	0.443	neutral	None	None	None	None	N
V/W	0.8693	likely_pathogenic	0.8146	pathogenic	-1.019	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
V/Y	0.6319	likely_pathogenic	0.5418	ambiguous	-0.725	Destabilizing	0.987	D	0.588	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.