TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13929	42010;42011;42012	chr2:178635539;178635538;178635537	chr2:179500266;179500265;179500264
N2AB	12288	37087;37088;37089	chr2:178635539;178635538;178635537	chr2:179500266;179500265;179500264
N2A	11361	34306;34307;34308	chr2:178635539;178635538;178635537	chr2:179500266;179500265;179500264
N2B	4864	14815;14816;14817	chr2:178635539;178635538;178635537	chr2:179500266;179500265;179500264
Novex-1	4989	15190;15191;15192	chr2:178635539;178635538;178635537	chr2:179500266;179500265;179500264
Novex-2	5056	15391;15392;15393	chr2:178635539;178635538;178635537	chr2:179500266;179500265;179500264
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: Ig-89
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.4151
• 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/Q	None	None	0.007	N	0.243	0.043	0.0551355673512	gnomAD-4.0.0	1.63521E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93708E-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	0.4902	ambiguous	0.6265	pathogenic	-0.718	Destabilizing	0.004	N	0.261	neutral	None	None	None	None	N
H/C	0.2438	likely_benign	0.3129	benign	0.118	Stabilizing	0.633	D	0.365	neutral	None	None	None	None	N
H/D	0.5812	likely_pathogenic	0.6889	pathogenic	-0.298	Destabilizing	None	N	0.16	neutral	N	0.444788607	None	None	N
H/E	0.4778	ambiguous	0.6047	pathogenic	-0.196	Destabilizing	None	N	0.063	neutral	None	None	None	None	N
H/F	0.4571	ambiguous	0.5794	pathogenic	0.436	Stabilizing	0.01	N	0.479	neutral	None	None	None	None	N
H/G	0.5881	likely_pathogenic	0.7121	pathogenic	-1.093	Destabilizing	0.009	N	0.278	neutral	None	None	None	None	N
H/I	0.395	ambiguous	0.5056	ambiguous	0.317	Stabilizing	0.021	N	0.511	neutral	None	None	None	None	N
H/K	0.2084	likely_benign	0.2326	benign	-0.369	Destabilizing	None	N	0.119	neutral	None	None	None	None	N
H/L	0.2276	likely_benign	0.2886	benign	0.317	Stabilizing	0.003	N	0.348	neutral	N	0.439536258	None	None	N
H/M	0.5865	likely_pathogenic	0.6876	pathogenic	0.171	Stabilizing	0.314	N	0.379	neutral	None	None	None	None	N
H/N	0.218	likely_benign	0.3121	benign	-0.446	Destabilizing	None	N	0.199	neutral	N	0.439292108	None	None	N
H/P	0.8643	likely_pathogenic	0.9016	pathogenic	-0.007	Destabilizing	0.031	N	0.459	neutral	N	0.447201085	None	None	N
H/Q	0.2107	likely_benign	0.2921	benign	-0.215	Destabilizing	0.007	N	0.243	neutral	N	0.443483213	None	None	N
H/R	0.0851	likely_benign	0.0976	benign	-0.835	Destabilizing	None	N	0.179	neutral	N	0.443682786	None	None	N
H/S	0.423	ambiguous	0.563	ambiguous	-0.541	Destabilizing	0.009	N	0.289	neutral	None	None	None	None	N
H/T	0.3659	ambiguous	0.5144	ambiguous	-0.329	Destabilizing	0.009	N	0.312	neutral	None	None	None	None	N
H/V	0.3596	ambiguous	0.4788	ambiguous	-0.007	Destabilizing	0.021	N	0.464	neutral	None	None	None	None	N
H/W	0.5965	likely_pathogenic	0.6554	pathogenic	0.743	Stabilizing	0.362	N	0.365	neutral	None	None	None	None	N
H/Y	0.1839	likely_benign	0.2587	benign	0.863	Stabilizing	None	N	0.173	neutral	N	0.448715659	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.