TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24649	74170;74171;74172	chr2:178572187;178572186;178572185	chr2:179436914;179436913;179436912
N2AB	23008	69247;69248;69249	chr2:178572187;178572186;178572185	chr2:179436914;179436913;179436912
N2A	22081	66466;66467;66468	chr2:178572187;178572186;178572185	chr2:179436914;179436913;179436912
N2B	15584	46975;46976;46977	chr2:178572187;178572186;178572185	chr2:179436914;179436913;179436912
Novex-1	15709	47350;47351;47352	chr2:178572187;178572186;178572185	chr2:179436914;179436913;179436912
Novex-2	15776	47551;47552;47553	chr2:178572187;178572186;178572185	chr2:179436914;179436913;179436912
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-67
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.2279
• 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
L/P	rs1559410802	None	0.995	N	0.703	0.383	0.802570031157	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66223E-04
L/P	rs1559410802	None	0.995	N	0.703	0.383	0.802570031157	gnomAD-4.0.0	1.36872E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79917E-06	0	0
L/V	None	None	0.068	N	0.477	0.042	0.423002944196	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
L/A	0.1397	likely_benign	0.1428	benign	-1.114	Destabilizing	0.833	D	0.549	neutral	None	None	None	None	N
L/C	0.487	ambiguous	0.4857	ambiguous	-0.655	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	N
L/D	0.6631	likely_pathogenic	0.6666	pathogenic	-0.57	Destabilizing	0.989	D	0.694	prob.neutral	None	None	None	None	N
L/E	0.3864	ambiguous	0.3959	ambiguous	-0.641	Destabilizing	0.985	D	0.687	prob.neutral	None	None	None	None	N
L/F	0.1564	likely_benign	0.1505	benign	-0.906	Destabilizing	0.972	D	0.506	neutral	None	None	None	None	N
L/G	0.3758	ambiguous	0.3789	ambiguous	-1.34	Destabilizing	0.989	D	0.625	neutral	None	None	None	None	N
L/H	0.217	likely_benign	0.217	benign	-0.51	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
L/I	0.0739	likely_benign	0.0722	benign	-0.616	Destabilizing	0.004	N	0.231	neutral	N	0.428881092	None	None	N
L/K	0.2898	likely_benign	0.2968	benign	-0.686	Destabilizing	0.556	D	0.577	neutral	None	None	None	None	N
L/M	0.0933	likely_benign	0.0947	benign	-0.469	Destabilizing	0.912	D	0.511	neutral	None	None	None	None	N
L/N	0.2617	likely_benign	0.2624	benign	-0.391	Destabilizing	0.989	D	0.703	prob.neutral	None	None	None	None	N
L/P	0.7149	likely_pathogenic	0.686	pathogenic	-0.749	Destabilizing	0.995	D	0.703	prob.neutral	N	0.488044689	None	None	N
L/Q	0.1478	likely_benign	0.1492	benign	-0.654	Destabilizing	0.988	D	0.669	neutral	N	0.470380998	None	None	N
L/R	0.2398	likely_benign	0.2379	benign	-0.026	Destabilizing	0.963	D	0.675	prob.neutral	N	0.496412806	None	None	N
L/S	0.1463	likely_benign	0.1462	benign	-0.907	Destabilizing	0.859	D	0.583	neutral	None	None	None	None	N
L/T	0.0829	likely_benign	0.0851	benign	-0.872	Destabilizing	0.02	N	0.221	neutral	None	None	None	None	N
L/V	0.0821	likely_benign	0.0823	benign	-0.749	Destabilizing	0.068	N	0.477	neutral	N	0.465281822	None	None	N
L/W	0.363	ambiguous	0.3255	benign	-0.891	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
L/Y	0.4011	ambiguous	0.3981	ambiguous	-0.686	Destabilizing	0.925	D	0.565	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.