TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8841	26746;26747;26748	chr2:178714137;178714136;178714135	chr2:179578864;179578863;179578862
N2AB	8524	25795;25796;25797	chr2:178714137;178714136;178714135	chr2:179578864;179578863;179578862
N2A	7597	23014;23015;23016	chr2:178714137;178714136;178714135	chr2:179578864;179578863;179578862
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-74
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.165
• 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/L	rs2154297041	None	0.962	N	0.455	0.369	0.602294275845	gnomAD-4.0.0	1.59262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86007E-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	0.2758	likely_benign	0.2958	benign	-1.614	Destabilizing	0.992	D	0.447	neutral	N	0.506857165	None	None	N
V/C	0.8523	likely_pathogenic	0.8535	pathogenic	-1.359	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
V/D	0.8425	likely_pathogenic	0.8454	pathogenic	-1.25	Destabilizing	1.0	D	0.717	prob.delet.	D	0.537245114	None	None	N
V/E	0.7701	likely_pathogenic	0.7526	pathogenic	-1.234	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
V/F	0.3524	ambiguous	0.3581	ambiguous	-1.344	Destabilizing	0.999	D	0.693	prob.neutral	D	0.52990128	None	None	N
V/G	0.3286	likely_benign	0.3406	ambiguous	-1.944	Destabilizing	1.0	D	0.701	prob.neutral	D	0.527521424	None	None	N
V/H	0.9059	likely_pathogenic	0.9138	pathogenic	-1.443	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
V/I	0.1114	likely_benign	0.1235	benign	-0.803	Destabilizing	0.619	D	0.313	neutral	D	0.526771077	None	None	N
V/K	0.8017	likely_pathogenic	0.7576	pathogenic	-1.163	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
V/L	0.385	ambiguous	0.4229	ambiguous	-0.803	Destabilizing	0.962	D	0.455	neutral	N	0.497412072	None	None	N
V/M	0.27	likely_benign	0.2966	benign	-0.749	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
V/N	0.713	likely_pathogenic	0.7333	pathogenic	-1.024	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
V/P	0.9419	likely_pathogenic	0.9471	pathogenic	-1.039	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
V/Q	0.7691	likely_pathogenic	0.7498	pathogenic	-1.187	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
V/R	0.7636	likely_pathogenic	0.7187	pathogenic	-0.715	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
V/S	0.4912	ambiguous	0.5366	ambiguous	-1.645	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
V/T	0.3503	ambiguous	0.3899	ambiguous	-1.508	Destabilizing	0.997	D	0.682	prob.neutral	None	None	None	None	N
V/W	0.948	likely_pathogenic	0.9598	pathogenic	-1.485	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
V/Y	0.8021	likely_pathogenic	0.7954	pathogenic	-1.174	Destabilizing	1.0	D	0.704	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.