TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19662	59209;59210;59211	chr2:178593224;178593223;178593222	chr2:179457951;179457950;179457949
N2AB	18021	54286;54287;54288	chr2:178593224;178593223;178593222	chr2:179457951;179457950;179457949
N2A	17094	51505;51506;51507	chr2:178593224;178593223;178593222	chr2:179457951;179457950;179457949
N2B	10597	32014;32015;32016	chr2:178593224;178593223;178593222	chr2:179457951;179457950;179457949
Novex-1	10722	32389;32390;32391	chr2:178593224;178593223;178593222	chr2:179457951;179457950;179457949
Novex-2	10789	32590;32591;32592	chr2:178593224;178593223;178593222	chr2:179457951;179457950;179457949
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-30
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.4473
• 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
I/T	None	None	0.324	N	0.481	0.139	0.460795861206	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	1.01626E-03	None	0	0	None	0	0	0	0	0
I/V	rs886055259	None	None	N	0.193	0.072	0.251639045875	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.93949E-04	None	0	0	0	0	0
I/V	rs886055259	None	None	N	0.193	0.072	0.251639045875	gnomAD-4.0.0	1.79432E-05	None	None	None	None	I	None	0	0	None	0	3.40351E-04	None	0	0	0	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
I/A	0.1653	likely_benign	0.1607	benign	-0.899	Destabilizing	0.004	N	0.325	neutral	None	None	None	None	I
I/C	0.4959	ambiguous	0.5323	ambiguous	-0.761	Destabilizing	0.818	D	0.575	neutral	None	None	None	None	I
I/D	0.6252	likely_pathogenic	0.6377	pathogenic	0.107	Stabilizing	0.818	D	0.628	neutral	None	None	None	None	I
I/E	0.431	ambiguous	0.4248	ambiguous	0.048	Stabilizing	0.563	D	0.611	neutral	None	None	None	None	I
I/F	0.1505	likely_benign	0.1599	benign	-0.704	Destabilizing	0.627	D	0.576	neutral	N	0.510534109	None	None	I
I/G	0.5338	ambiguous	0.5302	ambiguous	-1.114	Destabilizing	0.388	N	0.573	neutral	None	None	None	None	I
I/H	0.4161	ambiguous	0.425	ambiguous	-0.258	Destabilizing	0.981	D	0.623	neutral	None	None	None	None	I
I/K	0.2386	likely_benign	0.2343	benign	-0.353	Destabilizing	0.818	D	0.613	neutral	None	None	None	None	I
I/L	0.1108	likely_benign	0.1122	benign	-0.437	Destabilizing	0.041	N	0.237	neutral	N	0.438287222	None	None	I
I/M	0.105	likely_benign	0.1045	benign	-0.442	Destabilizing	0.627	D	0.587	neutral	N	0.503685495	None	None	I
I/N	0.2474	likely_benign	0.2575	benign	-0.158	Destabilizing	0.912	D	0.631	neutral	N	0.519460237	None	None	I
I/P	0.4038	ambiguous	0.4221	ambiguous	-0.557	Destabilizing	0.818	D	0.629	neutral	None	None	None	None	I
I/Q	0.3193	likely_benign	0.3171	benign	-0.361	Destabilizing	0.932	D	0.631	neutral	None	None	None	None	I
I/R	0.1879	likely_benign	0.1847	benign	0.183	Stabilizing	0.818	D	0.631	neutral	None	None	None	None	I
I/S	0.2123	likely_benign	0.2067	benign	-0.777	Destabilizing	0.193	N	0.581	neutral	N	0.49223635	None	None	I
I/T	0.0896	likely_benign	0.0874	benign	-0.717	Destabilizing	0.324	N	0.481	neutral	N	0.450216369	None	None	I
I/V	0.0661	likely_benign	0.0657	benign	-0.557	Destabilizing	None	N	0.193	neutral	N	0.406580235	None	None	I
I/W	0.6651	likely_pathogenic	0.6868	pathogenic	-0.668	Destabilizing	0.981	D	0.657	neutral	None	None	None	None	I
I/Y	0.4234	ambiguous	0.4564	ambiguous	-0.43	Destabilizing	0.818	D	0.587	neutral	None	None	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.