TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18065	54418;54419;54420	chr2:178604896;178604895;178604894	chr2:179469623;179469622;179469621
N2AB	16424	49495;49496;49497	chr2:178604896;178604895;178604894	chr2:179469623;179469622;179469621
N2A	15497	46714;46715;46716	chr2:178604896;178604895;178604894	chr2:179469623;179469622;179469621
N2B	9000	27223;27224;27225	chr2:178604896;178604895;178604894	chr2:179469623;179469622;179469621
Novex-1	9125	27598;27599;27600	chr2:178604896;178604895;178604894	chr2:179469623;179469622;179469621
Novex-2	9192	27799;27800;27801	chr2:178604896;178604895;178604894	chr2:179469623;179469622;179469621
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-19
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4
• 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
R/C	rs369438623	-0.759	1.0	N	0.873	0.418	None	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	6.49E-05	2.94E-05	None	0	5.66E-05	None	0	None	0	0	0
R/C	rs369438623	-0.759	1.0	N	0.873	0.418	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.42E-05	6.57E-05	0	0	0	None	0	0	0	0	0
R/C	rs369438623	-0.759	1.0	N	0.873	0.418	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/C	rs369438623	-0.759	1.0	N	0.873	0.418	None	gnomAD-4.0.0	7.45221E-06	None	None	None	None	I	None	4.01273E-05	5.03423E-05	None	0	0	None	0	0	1.69765E-06	3.3125E-05	1.60462E-05
R/H	rs375895183	-1.416	1.0	N	0.753	0.353	None	gnomAD-2.1.1	6.5E-05	None	None	None	None	I	None	0	5.86E-05	None	0	2.82358E-04	None	0	None	4.68E-05	7.18E-05	0
R/H	rs375895183	-1.416	1.0	N	0.753	0.353	None	gnomAD-3.1.2	4.61E-05	None	None	None	None	I	None	2.42E-05	6.57E-05	0	0	3.90625E-04	None	0	0	4.42E-05	0	0
R/H	rs375895183	-1.416	1.0	N	0.753	0.353	None	gnomAD-4.0.0	9.19224E-05	None	None	None	None	I	None	1.33933E-05	6.70848E-05	None	3.39466E-05	2.01712E-04	None	0	0	1.09502E-04	2.21078E-05	3.21007E-05
R/P	rs375895183	None	1.0	N	0.826	0.439	0.350088858571	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/P	rs375895183	None	1.0	N	0.826	0.439	0.350088858571	gnomAD-4.0.0	6.59092E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47306E-05	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
R/A	0.763	likely_pathogenic	0.6725	pathogenic	-0.312	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	I
R/C	0.333	likely_benign	0.2563	benign	-0.279	Destabilizing	1.0	D	0.873	deleterious	N	0.469049882	None	None	I
R/D	0.9742	likely_pathogenic	0.9582	pathogenic	-0.06	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
R/E	0.7897	likely_pathogenic	0.706	pathogenic	0.002	Stabilizing	0.998	D	0.651	prob.neutral	None	None	None	None	I
R/F	0.8897	likely_pathogenic	0.8309	pathogenic	-0.494	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
R/G	0.8127	likely_pathogenic	0.7173	pathogenic	-0.526	Destabilizing	1.0	D	0.713	prob.delet.	N	0.486482574	None	None	I
R/H	0.3105	likely_benign	0.2509	benign	-0.918	Destabilizing	1.0	D	0.753	deleterious	N	0.468796393	None	None	I
R/I	0.4742	ambiguous	0.376	ambiguous	0.225	Stabilizing	0.999	D	0.856	deleterious	None	None	None	None	I
R/K	0.1476	likely_benign	0.1438	benign	-0.306	Destabilizing	0.995	D	0.525	neutral	None	None	None	None	I
R/L	0.6062	likely_pathogenic	0.5018	ambiguous	0.225	Stabilizing	1.0	D	0.713	prob.delet.	N	0.510925606	None	None	I
R/M	0.649	likely_pathogenic	0.5556	ambiguous	-0.018	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
R/N	0.9144	likely_pathogenic	0.8736	pathogenic	0.148	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
R/P	0.85	likely_pathogenic	0.809	pathogenic	0.066	Stabilizing	1.0	D	0.826	deleterious	N	0.479215833	None	None	I
R/Q	0.233	likely_benign	0.1885	benign	-0.076	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
R/S	0.8735	likely_pathogenic	0.809	pathogenic	-0.394	Destabilizing	1.0	D	0.763	deleterious	N	0.509522884	None	None	I
R/T	0.61	likely_pathogenic	0.4977	ambiguous	-0.193	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
R/V	0.5331	ambiguous	0.4449	ambiguous	0.066	Stabilizing	0.999	D	0.801	deleterious	None	None	None	None	I
R/W	0.6567	likely_pathogenic	0.5584	ambiguous	-0.394	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
R/Y	0.7985	likely_pathogenic	0.7263	pathogenic	-0.021	Destabilizing	0.999	D	0.886	deleterious	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.