TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7602	23029;23030;23031	chr2:178721859;178721858;178721857	chr2:179586586;179586585;179586584
N2AB	7285	22078;22079;22080	chr2:178721859;178721858;178721857	chr2:179586586;179586585;179586584
N2A	6358	19297;19298;19299	chr2:178721859;178721858;178721857	chr2:179586586;179586585;179586584
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-60
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0912
• 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
L/F	rs754142672	-1.765	0.998	N	0.739	0.479	0.646549884328	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	0
L/F	rs754142672	-1.765	0.998	N	0.739	0.479	0.646549884328	gnomAD-4.0.0	3.21054E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89172E-05	0	2.88033E-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
L/A	0.9563	likely_pathogenic	0.9598	pathogenic	-2.841	Highly Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
L/C	0.9659	likely_pathogenic	0.9606	pathogenic	-2.437	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.138	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9981	pathogenic	-2.844	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/F	0.8421	likely_pathogenic	0.8527	pathogenic	-1.786	Destabilizing	0.998	D	0.739	prob.delet.	N	0.509603027	None	None	N
L/G	0.9916	likely_pathogenic	0.9922	pathogenic	-3.452	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/H	0.9958	likely_pathogenic	0.9966	pathogenic	-2.994	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.556460281	None	None	N
L/I	0.2283	likely_benign	0.2586	benign	-1.024	Destabilizing	0.753	D	0.613	neutral	N	0.493305517	None	None	N
L/K	0.9968	likely_pathogenic	0.9975	pathogenic	-2.086	Highly Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
L/M	0.5106	ambiguous	0.5209	ambiguous	-1.248	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
L/N	0.9976	likely_pathogenic	0.9979	pathogenic	-2.647	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/P	0.9977	likely_pathogenic	0.998	pathogenic	-1.617	Destabilizing	1.0	D	0.848	deleterious	D	0.556460281	None	None	N
L/Q	0.992	likely_pathogenic	0.994	pathogenic	-2.376	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/R	0.9917	likely_pathogenic	0.9938	pathogenic	-2.005	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.556460281	None	None	N
L/S	0.996	likely_pathogenic	0.9967	pathogenic	-3.393	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/T	0.9785	likely_pathogenic	0.9805	pathogenic	-2.927	Highly Destabilizing	0.719	D	0.547	neutral	None	None	None	None	N
L/V	0.242	likely_benign	0.2649	benign	-1.617	Destabilizing	0.097	N	0.342	neutral	N	0.499493183	None	None	N
L/W	0.99	likely_pathogenic	0.9923	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/Y	0.9885	likely_pathogenic	0.9898	pathogenic	-1.904	Destabilizing	0.996	D	0.746	deleterious	None	None	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.