TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32317	97174;97175;97176	chr2:178542905;178542904;178542903	chr2:179407632;179407631;179407630
N2AB	30676	92251;92252;92253	chr2:178542905;178542904;178542903	chr2:179407632;179407631;179407630
N2A	29749	89470;89471;89472	chr2:178542905;178542904;178542903	chr2:179407632;179407631;179407630
N2B	23252	69979;69980;69981	chr2:178542905;178542904;178542903	chr2:179407632;179407631;179407630
Novex-1	23377	70354;70355;70356	chr2:178542905;178542904;178542903	chr2:179407632;179407631;179407630
Novex-2	23444	70555;70556;70557	chr2:178542905;178542904;178542903	chr2:179407632;179407631;179407630
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-154
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.7584
• Predicted PPI site: I

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/D	rs779019939	-0.415	0.852	N	0.343	0.207	0.256283259241	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
H/D	rs779019939	-0.415	0.852	N	0.343	0.207	0.256283259241	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/D	rs779019939	-0.415	0.852	N	0.343	0.207	0.256283259241	gnomAD-4.0.0	3.84689E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.18976E-06	0	0
H/Y	None	None	0.134	N	0.244	0.16	0.239901079897	gnomAD-4.0.0	1.5931E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43345E-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
H/A	0.4564	ambiguous	0.3847	ambiguous	-0.4	Destabilizing	0.939	D	0.341	neutral	None	None	None	None	I
H/C	0.2973	likely_benign	0.2467	benign	0.149	Stabilizing	0.999	D	0.383	neutral	None	None	None	None	I
H/D	0.6962	likely_pathogenic	0.4479	ambiguous	-0.648	Destabilizing	0.852	D	0.343	neutral	N	0.467063839	None	None	I
H/E	0.7156	likely_pathogenic	0.5914	pathogenic	-0.562	Destabilizing	0.884	D	0.299	neutral	None	None	None	None	I
H/F	0.414	ambiguous	0.3272	benign	0.822	Stabilizing	0.964	D	0.386	neutral	None	None	None	None	I
H/G	0.6379	likely_pathogenic	0.54	ambiguous	-0.744	Destabilizing	0.939	D	0.364	neutral	None	None	None	None	I
H/I	0.4229	ambiguous	0.3301	benign	0.535	Stabilizing	0.991	D	0.379	neutral	None	None	None	None	I
H/K	0.7052	likely_pathogenic	0.5853	pathogenic	-0.461	Destabilizing	0.884	D	0.351	neutral	None	None	None	None	I
H/L	0.2131	likely_benign	0.1576	benign	0.535	Stabilizing	0.92	D	0.405	neutral	N	0.437781082	None	None	I
H/M	0.5401	ambiguous	0.4948	ambiguous	0.256	Stabilizing	0.999	D	0.344	neutral	None	None	None	None	I
H/N	0.1454	likely_benign	0.1215	benign	-0.735	Destabilizing	0.134	N	0.193	neutral	N	0.414712221	None	None	I
H/P	0.3594	ambiguous	0.2851	benign	0.245	Stabilizing	0.996	D	0.369	neutral	N	0.486516391	None	None	I
H/Q	0.3981	ambiguous	0.3264	benign	-0.503	Destabilizing	0.509	D	0.235	neutral	N	0.447862002	None	None	I
H/R	0.4089	ambiguous	0.2847	benign	-1.037	Destabilizing	0.92	D	0.331	neutral	N	0.412653351	None	None	I
H/S	0.2837	likely_benign	0.2487	benign	-0.611	Destabilizing	0.939	D	0.357	neutral	None	None	None	None	I
H/T	0.3323	likely_benign	0.2739	benign	-0.418	Destabilizing	0.939	D	0.369	neutral	None	None	None	None	I
H/V	0.3353	likely_benign	0.2632	benign	0.245	Stabilizing	0.939	D	0.385	neutral	None	None	None	None	I
H/W	0.5469	ambiguous	0.4392	ambiguous	1.042	Stabilizing	0.999	D	0.355	neutral	None	None	None	None	I
H/Y	0.1524	likely_benign	0.106	benign	1.104	Stabilizing	0.134	N	0.244	neutral	N	0.419446037	None	None	I

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.