TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6377	19354;19355;19356	chr2:178728909;178728908;178728907	chr2:179593636;179593635;179593634
N2AB	6060	18403;18404;18405	chr2:178728909;178728908;178728907	chr2:179593636;179593635;179593634
N2A	5133	15622;15623;15624	chr2:178728909;178728908;178728907	chr2:179593636;179593635;179593634
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-47
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0753
• 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
A/T	None	None	0.984	N	0.641	0.447	0.615206833243	gnomAD-4.0.0	1.37633E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80652E-06	0	0
A/V	None	None	0.996	N	0.659	0.39	0.645897206421	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
A/C	0.8958	likely_pathogenic	0.8603	pathogenic	-0.386	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
A/D	0.9779	likely_pathogenic	0.9801	pathogenic	-1.203	Destabilizing	0.998	D	0.866	deleterious	D	0.569842319	None	None	N
A/E	0.9895	likely_pathogenic	0.9898	pathogenic	-1.009	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
A/F	0.978	likely_pathogenic	0.977	pathogenic	-0.344	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
A/G	0.1238	likely_benign	0.1232	benign	-1.008	Destabilizing	0.992	D	0.576	neutral	N	0.512642718	None	None	N
A/H	0.9905	likely_pathogenic	0.9899	pathogenic	-1.552	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/I	0.9672	likely_pathogenic	0.9637	pathogenic	0.739	Stabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
A/K	0.9963	likely_pathogenic	0.9966	pathogenic	-0.485	Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
A/L	0.9294	likely_pathogenic	0.9258	pathogenic	0.739	Stabilizing	0.997	D	0.775	deleterious	None	None	None	None	N
A/M	0.9498	likely_pathogenic	0.9458	pathogenic	0.509	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/N	0.9586	likely_pathogenic	0.9603	pathogenic	-0.717	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
A/P	0.9912	likely_pathogenic	0.9904	pathogenic	0.363	Stabilizing	0.999	D	0.871	deleterious	D	0.569842319	None	None	N
A/Q	0.9797	likely_pathogenic	0.9808	pathogenic	-0.484	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
A/R	0.9861	likely_pathogenic	0.9869	pathogenic	-0.779	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
A/S	0.1697	likely_benign	0.1688	benign	-1.186	Destabilizing	0.916	D	0.377	neutral	N	0.499525213	None	None	N
A/T	0.5829	likely_pathogenic	0.5568	ambiguous	-0.85	Destabilizing	0.984	D	0.641	neutral	N	0.497790466	None	None	N
A/V	0.8422	likely_pathogenic	0.8293	pathogenic	0.363	Stabilizing	0.996	D	0.659	neutral	N	0.488556847	None	None	N
A/W	0.9983	likely_pathogenic	0.998	pathogenic	-1.116	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
A/Y	0.9896	likely_pathogenic	0.9882	pathogenic	-0.446	Destabilizing	1.0	D	0.889	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.