TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16888	50887;50888;50889	chr2:178611567;178611566;178611565	chr2:179476294;179476293;179476292
N2AB	15247	45964;45965;45966	chr2:178611567;178611566;178611565	chr2:179476294;179476293;179476292
N2A	14320	43183;43184;43185	chr2:178611567;178611566;178611565	chr2:179476294;179476293;179476292
N2B	7823	23692;23693;23694	chr2:178611567;178611566;178611565	chr2:179476294;179476293;179476292
Novex-1	7948	24067;24068;24069	chr2:178611567;178611566;178611565	chr2:179476294;179476293;179476292
Novex-2	8015	24268;24269;24270	chr2:178611567;178611566;178611565	chr2:179476294;179476293;179476292
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-11
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2666
• 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
H/R	None	None	0.896	N	0.654	0.409	0.289098819767	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
H/Y	None	None	0.995	N	0.653	0.312	0.342865806769	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
H/A	0.8303	likely_pathogenic	0.8188	pathogenic	-1.679	Destabilizing	0.919	D	0.663	neutral	None	None	None	None	N
H/C	0.4992	ambiguous	0.5019	ambiguous	-1.118	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
H/D	0.807	likely_pathogenic	0.8426	pathogenic	-1.64	Destabilizing	0.811	D	0.637	neutral	N	0.461441129	None	None	N
H/E	0.8381	likely_pathogenic	0.8519	pathogenic	-1.484	Destabilizing	0.919	D	0.627	neutral	None	None	None	None	N
H/F	0.513	ambiguous	0.5065	ambiguous	0.033	Stabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
H/G	0.9282	likely_pathogenic	0.9326	pathogenic	-2.042	Highly Destabilizing	0.851	D	0.663	neutral	None	None	None	None	N
H/I	0.5858	likely_pathogenic	0.552	ambiguous	-0.623	Destabilizing	0.988	D	0.793	deleterious	None	None	None	None	N
H/K	0.9222	likely_pathogenic	0.9146	pathogenic	-1.533	Destabilizing	0.919	D	0.67	neutral	None	None	None	None	N
H/L	0.3273	likely_benign	0.3152	benign	-0.623	Destabilizing	0.984	D	0.739	prob.delet.	N	0.45930798	None	None	N
H/M	0.7351	likely_pathogenic	0.723	pathogenic	-0.871	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
H/N	0.2555	likely_benign	0.2672	benign	-1.829	Destabilizing	0.011	N	0.401	neutral	N	0.470016679	None	None	N
H/P	0.9749	likely_pathogenic	0.9684	pathogenic	-0.963	Destabilizing	0.995	D	0.732	prob.delet.	D	0.547806723	None	None	N
H/Q	0.6615	likely_pathogenic	0.6565	pathogenic	-1.421	Destabilizing	0.984	D	0.659	neutral	N	0.466055256	None	None	N
H/R	0.7628	likely_pathogenic	0.7524	pathogenic	-1.869	Destabilizing	0.896	D	0.654	neutral	N	0.458321952	None	None	N
H/S	0.6257	likely_pathogenic	0.6343	pathogenic	-1.924	Destabilizing	0.851	D	0.637	neutral	None	None	None	None	N
H/T	0.7112	likely_pathogenic	0.6977	pathogenic	-1.669	Destabilizing	0.919	D	0.687	prob.neutral	None	None	None	None	N
H/V	0.5819	likely_pathogenic	0.5454	ambiguous	-0.963	Destabilizing	0.988	D	0.755	deleterious	None	None	None	None	N
H/W	0.6324	likely_pathogenic	0.6958	pathogenic	0.369	Stabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
H/Y	0.2057	likely_benign	0.2249	benign	0.275	Stabilizing	0.995	D	0.653	neutral	N	0.472579732	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.