TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28934	87025;87026;87027	chr2:178559332;178559331;178559330	chr2:179424059;179424058;179424057
N2AB	27293	82102;82103;82104	chr2:178559332;178559331;178559330	chr2:179424059;179424058;179424057
N2A	26366	79321;79322;79323	chr2:178559332;178559331;178559330	chr2:179424059;179424058;179424057
N2B	19869	59830;59831;59832	chr2:178559332;178559331;178559330	chr2:179424059;179424058;179424057
Novex-1	19994	60205;60206;60207	chr2:178559332;178559331;178559330	chr2:179424059;179424058;179424057
Novex-2	20061	60406;60407;60408	chr2:178559332;178559331;178559330	chr2:179424059;179424058;179424057
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-98
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.9263
• 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
K/N	rs1280845808	0.15	0.986	N	0.705	0.188	0.143124449307	gnomAD-2.1.1	4.24E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.67E-05	None	0	0	0
K/N	rs1280845808	0.15	0.986	N	0.705	0.188	0.143124449307	gnomAD-4.0.0	1.38871E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.42266E-05	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
K/A	0.1903	likely_benign	0.1976	benign	-0.013	Destabilizing	0.963	D	0.532	neutral	None	None	None	None	N
K/C	0.5659	likely_pathogenic	0.5678	pathogenic	-0.511	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/D	0.403	ambiguous	0.3896	ambiguous	-0.374	Destabilizing	0.989	D	0.639	neutral	None	None	None	None	N
K/E	0.1252	likely_benign	0.1151	benign	-0.394	Destabilizing	0.908	D	0.517	neutral	N	0.460563862	None	None	N
K/F	0.6965	likely_pathogenic	0.6861	pathogenic	-0.379	Destabilizing	1.0	D	0.701	prob.delet.	None	None	None	None	N
K/G	0.2452	likely_benign	0.2378	benign	-0.119	Destabilizing	0.989	D	0.491	neutral	None	None	None	None	N
K/H	0.303	likely_benign	0.2997	benign	-0.179	Destabilizing	0.999	D	0.663	prob.neutral	None	None	None	None	N
K/I	0.3033	likely_benign	0.2976	benign	0.184	Stabilizing	0.995	D	0.731	deleterious	None	None	None	None	N
K/L	0.2561	likely_benign	0.263	benign	0.184	Stabilizing	0.989	D	0.491	neutral	None	None	None	None	N
K/M	0.2035	likely_benign	0.2022	benign	-0.168	Destabilizing	0.998	D	0.663	prob.neutral	N	0.474439296	None	None	N
K/N	0.3235	likely_benign	0.3199	benign	-0.051	Destabilizing	0.986	D	0.705	prob.delet.	N	0.514686348	None	None	N
K/P	0.3146	likely_benign	0.3312	benign	0.14	Stabilizing	0.995	D	0.708	prob.delet.	None	None	None	None	N
K/Q	0.1151	likely_benign	0.1137	benign	-0.198	Destabilizing	0.379	N	0.327	neutral	N	0.474185806	None	None	N
K/R	0.0768	likely_benign	0.0735	benign	-0.155	Destabilizing	0.908	D	0.521	neutral	N	0.484710158	None	None	N
K/S	0.2475	likely_benign	0.2532	benign	-0.396	Destabilizing	0.963	D	0.583	neutral	None	None	None	None	N
K/T	0.1209	likely_benign	0.1238	benign	-0.312	Destabilizing	0.986	D	0.656	prob.neutral	N	0.42235219	None	None	N
K/V	0.2358	likely_benign	0.2333	benign	0.14	Stabilizing	0.989	D	0.627	neutral	None	None	None	None	N
K/W	0.6654	likely_pathogenic	0.6527	pathogenic	-0.492	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/Y	0.5986	likely_pathogenic	0.5818	pathogenic	-0.147	Destabilizing	0.998	D	0.663	prob.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.