TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6390	19393;19394;19395	chr2:178728758;178728757;178728756	chr2:179593485;179593484;179593483
N2AB	6073	18442;18443;18444	chr2:178728758;178728757;178728756	chr2:179593485;179593484;179593483
N2A	5146	15661;15662;15663	chr2:178728758;178728757;178728756	chr2:179593485;179593484;179593483
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-48
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6384
• 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
K/E	rs1220495372	0.308	0.977	N	0.572	0.38	0.390060412749	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
K/E	rs1220495372	0.308	0.977	N	0.572	0.38	0.390060412749	gnomAD-4.0.0	1.62319E-06	None	None	None	None	N	None	0	2.30404E-05	None	0	0	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
K/A	0.384	ambiguous	0.3846	ambiguous	-0.142	Destabilizing	0.983	D	0.632	neutral	None	None	None	None	N
K/C	0.8269	likely_pathogenic	0.8261	pathogenic	-0.228	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/D	0.6037	likely_pathogenic	0.6212	pathogenic	0.11	Stabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
K/E	0.1646	likely_benign	0.1787	benign	0.142	Stabilizing	0.977	D	0.572	neutral	N	0.492943718	None	None	N
K/F	0.8128	likely_pathogenic	0.8134	pathogenic	-0.19	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
K/G	0.5527	ambiguous	0.5573	ambiguous	-0.397	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
K/H	0.407	ambiguous	0.4017	ambiguous	-0.753	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
K/I	0.4488	ambiguous	0.4431	ambiguous	0.467	Stabilizing	0.997	D	0.759	deleterious	N	0.491239418	None	None	N
K/L	0.437	ambiguous	0.4371	ambiguous	0.467	Stabilizing	0.995	D	0.643	neutral	None	None	None	None	N
K/M	0.2433	likely_benign	0.2484	benign	0.284	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/N	0.4314	ambiguous	0.4514	ambiguous	0.103	Stabilizing	0.993	D	0.697	prob.neutral	N	0.489063826	None	None	N
K/P	0.5354	ambiguous	0.5243	ambiguous	0.293	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
K/Q	0.15	likely_benign	0.1471	benign	-0.056	Destabilizing	0.993	D	0.687	prob.neutral	N	0.509817325	None	None	N
K/R	0.0939	likely_benign	0.0946	benign	-0.215	Destabilizing	0.235	N	0.261	neutral	N	0.502891353	None	None	N
K/S	0.4886	ambiguous	0.5058	ambiguous	-0.438	Destabilizing	0.983	D	0.637	neutral	None	None	None	None	N
K/T	0.2046	likely_benign	0.2103	benign	-0.238	Destabilizing	0.997	D	0.728	prob.delet.	N	0.486163763	None	None	N
K/V	0.4086	ambiguous	0.4087	ambiguous	0.293	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
K/W	0.8118	likely_pathogenic	0.8272	pathogenic	-0.146	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
K/Y	0.6588	likely_pathogenic	0.6706	pathogenic	0.182	Stabilizing	0.999	D	0.741	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.