TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19364	58315;58316;58317	chr2:178594404;178594403;178594402	chr2:179459131;179459130;179459129
N2AB	17723	53392;53393;53394	chr2:178594404;178594403;178594402	chr2:179459131;179459130;179459129
N2A	16796	50611;50612;50613	chr2:178594404;178594403;178594402	chr2:179459131;179459130;179459129
N2B	10299	31120;31121;31122	chr2:178594404;178594403;178594402	chr2:179459131;179459130;179459129
Novex-1	10424	31495;31496;31497	chr2:178594404;178594403;178594402	chr2:179459131;179459130;179459129
Novex-2	10491	31696;31697;31698	chr2:178594404;178594403;178594402	chr2:179459131;179459130;179459129
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: Fn3-28
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.6127
• 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/M	rs182489815	-0.303	0.988	N	0.307	0.151	None	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	6.49E-05	0	None	0	0	None	0	None	0	0	0
I/M	rs182489815	-0.303	0.988	N	0.307	0.151	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/M	rs182489815	-0.303	0.988	N	0.307	0.151	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/M	rs182489815	-0.303	0.988	N	0.307	0.151	None	gnomAD-4.0.0	1.31392E-05	None	None	None	None	I	None	4.81255E-05	0	None	0	0	None	0	0	0	0	0
I/N	rs1239668517	0.074	0.988	N	0.491	0.356	0.757756501284	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
I/N	rs1239668517	0.074	0.988	N	0.491	0.356	0.757756501284	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
I/N	rs1239668517	0.074	0.988	N	0.491	0.356	0.757756501284	gnomAD-4.0.0	4.35677E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.9529E-06	0	0
I/V	rs1472130936	-0.084	0.061	N	0.12	0.079	0.400613892164	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.43E-05	None	0	0	0
I/V	rs1472130936	-0.084	0.061	N	0.12	0.079	0.400613892164	gnomAD-4.0.0	3.21792E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.91724E-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
I/A	0.1643	likely_benign	0.1985	benign	-0.641	Destabilizing	0.863	D	0.437	neutral	None	None	None	None	I
I/C	0.629	likely_pathogenic	0.7019	pathogenic	-0.876	Destabilizing	0.999	D	0.393	neutral	None	None	None	None	I
I/D	0.5397	ambiguous	0.5875	pathogenic	-0.078	Destabilizing	0.884	D	0.543	neutral	None	None	None	None	I
I/E	0.3052	likely_benign	0.3744	ambiguous	-0.154	Destabilizing	0.17	N	0.283	neutral	None	None	None	None	I
I/F	0.2277	likely_benign	0.2332	benign	-0.545	Destabilizing	0.988	D	0.302	neutral	N	0.518980234	None	None	I
I/G	0.5149	ambiguous	0.5929	pathogenic	-0.8	Destabilizing	0.969	D	0.503	neutral	None	None	None	None	I
I/H	0.4668	ambiguous	0.5132	ambiguous	0.015	Stabilizing	0.991	D	0.471	neutral	None	None	None	None	I
I/K	0.2772	likely_benign	0.3013	benign	-0.418	Destabilizing	0.884	D	0.528	neutral	None	None	None	None	I
I/L	0.1191	likely_benign	0.1254	benign	-0.343	Destabilizing	0.509	D	0.234	neutral	N	0.453083316	None	None	I
I/M	0.0912	likely_benign	0.0982	benign	-0.504	Destabilizing	0.988	D	0.307	neutral	N	0.481539354	None	None	I
I/N	0.2549	likely_benign	0.2832	benign	-0.372	Destabilizing	0.988	D	0.491	neutral	N	0.461566726	None	None	I
I/P	0.6087	likely_pathogenic	0.6305	pathogenic	-0.41	Destabilizing	0.997	D	0.49	neutral	None	None	None	None	I
I/Q	0.3	likely_benign	0.352	ambiguous	-0.55	Destabilizing	0.2	N	0.264	neutral	None	None	None	None	I
I/R	0.257	likely_benign	0.2624	benign	0.123	Stabilizing	0.939	D	0.493	neutral	None	None	None	None	I
I/S	0.216	likely_benign	0.2511	benign	-0.849	Destabilizing	0.92	D	0.495	neutral	N	0.380855071	None	None	I
I/T	0.128	likely_benign	0.1413	benign	-0.814	Destabilizing	0.92	D	0.422	neutral	N	0.451176374	None	None	I
I/V	0.0686	likely_benign	0.0699	benign	-0.41	Destabilizing	0.061	N	0.12	neutral	N	0.430398457	None	None	I
I/W	0.8247	likely_pathogenic	0.8212	pathogenic	-0.547	Destabilizing	0.999	D	0.501	neutral	None	None	None	None	I
I/Y	0.5689	likely_pathogenic	0.5832	pathogenic	-0.32	Destabilizing	0.997	D	0.411	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.