TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22826	68701;68702;68703	chr2:178578039;178578038;178578037	chr2:179442766;179442765;179442764
N2AB	21185	63778;63779;63780	chr2:178578039;178578038;178578037	chr2:179442766;179442765;179442764
N2A	20258	60997;60998;60999	chr2:178578039;178578038;178578037	chr2:179442766;179442765;179442764
N2B	13761	41506;41507;41508	chr2:178578039;178578038;178578037	chr2:179442766;179442765;179442764
Novex-1	13886	41881;41882;41883	chr2:178578039;178578038;178578037	chr2:179442766;179442765;179442764
Novex-2	13953	42082;42083;42084	chr2:178578039;178578038;178578037	chr2:179442766;179442765;179442764
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-53
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3495
• 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
V/M	rs1399440525	-0.592	0.968	N	0.705	0.131	0.382087116544	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
V/M	rs1399440525	-0.592	0.968	N	0.705	0.131	0.382087116544	gnomAD-4.0.0	1.36889E-06	None	None	None	None	I	None	0	4.47287E-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
V/A	0.1689	likely_benign	0.1666	benign	-1.337	Destabilizing	0.78	D	0.575	neutral	N	0.48118985	None	None	I
V/C	0.7121	likely_pathogenic	0.6811	pathogenic	-0.823	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
V/D	0.6048	likely_pathogenic	0.6245	pathogenic	-1.079	Destabilizing	0.996	D	0.836	deleterious	None	None	None	None	I
V/E	0.4196	ambiguous	0.4423	ambiguous	-1.129	Destabilizing	0.995	D	0.84	deleterious	N	0.486787671	None	None	I
V/F	0.2298	likely_benign	0.2316	benign	-1.175	Destabilizing	0.976	D	0.775	deleterious	None	None	None	None	I
V/G	0.3619	ambiguous	0.3542	ambiguous	-1.602	Destabilizing	0.995	D	0.825	deleterious	N	0.46337616	None	None	I
V/H	0.7169	likely_pathogenic	0.7212	pathogenic	-1.087	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
V/I	0.0658	likely_benign	0.0629	benign	-0.731	Destabilizing	0.034	N	0.279	neutral	None	None	None	None	I
V/K	0.5344	ambiguous	0.549	ambiguous	-1.053	Destabilizing	0.988	D	0.829	deleterious	None	None	None	None	I
V/L	0.1974	likely_benign	0.1826	benign	-0.731	Destabilizing	0.011	N	0.297	neutral	N	0.425277852	None	None	I
V/M	0.1408	likely_benign	0.1378	benign	-0.495	Destabilizing	0.968	D	0.705	prob.neutral	N	0.495620585	None	None	I
V/N	0.3973	ambiguous	0.3845	ambiguous	-0.734	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	I
V/P	0.4658	ambiguous	0.417	ambiguous	-0.898	Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	I
V/Q	0.449	ambiguous	0.4596	ambiguous	-0.981	Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	I
V/R	0.5027	ambiguous	0.5191	ambiguous	-0.457	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	I
V/S	0.2708	likely_benign	0.2656	benign	-1.217	Destabilizing	0.988	D	0.815	deleterious	None	None	None	None	I
V/T	0.14	likely_benign	0.1366	benign	-1.164	Destabilizing	0.919	D	0.61	neutral	None	None	None	None	I
V/W	0.8493	likely_pathogenic	0.8518	pathogenic	-1.282	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
V/Y	0.6517	likely_pathogenic	0.6429	pathogenic	-1.018	Destabilizing	0.996	D	0.773	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.