TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19680	59263;59264;59265	chr2:178593081;178593080;178593079	chr2:179457808;179457807;179457806
N2AB	18039	54340;54341;54342	chr2:178593081;178593080;178593079	chr2:179457808;179457807;179457806
N2A	17112	51559;51560;51561	chr2:178593081;178593080;178593079	chr2:179457808;179457807;179457806
N2B	10615	32068;32069;32070	chr2:178593081;178593080;178593079	chr2:179457808;179457807;179457806
Novex-1	10740	32443;32444;32445	chr2:178593081;178593080;178593079	chr2:179457808;179457807;179457806
Novex-2	10807	32644;32645;32646	chr2:178593081;178593080;178593079	chr2:179457808;179457807;179457806
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: Fn3-31
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6483
• 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
K/E	rs2050579789	None	0.992	N	0.624	0.167	0.27479166964	gnomAD-4.0.0	1.59735E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86338E-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
K/A	0.3511	ambiguous	0.3694	ambiguous	-0.273	Destabilizing	0.964	D	0.513	neutral	None	None	None	None	I
K/C	0.6182	likely_pathogenic	0.6813	pathogenic	-0.287	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
K/D	0.8132	likely_pathogenic	0.8302	pathogenic	-0.033	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	I
K/E	0.3028	likely_benign	0.2897	benign	-0.026	Destabilizing	0.992	D	0.624	neutral	N	0.465855038	None	None	I
K/F	0.7865	likely_pathogenic	0.8143	pathogenic	-0.538	Destabilizing	0.995	D	0.839	deleterious	None	None	None	None	I
K/G	0.6705	likely_pathogenic	0.6818	pathogenic	-0.498	Destabilizing	0.998	D	0.526	neutral	None	None	None	None	I
K/H	0.4897	ambiguous	0.5148	ambiguous	-0.944	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
K/I	0.2294	likely_benign	0.2628	benign	0.247	Stabilizing	0.386	N	0.475	neutral	N	0.473935804	None	None	I
K/L	0.2735	likely_benign	0.2943	benign	0.247	Stabilizing	0.931	D	0.523	neutral	None	None	None	None	I
K/M	0.2262	likely_benign	0.2488	benign	0.384	Stabilizing	0.999	D	0.599	neutral	None	None	None	None	I
K/N	0.6359	likely_pathogenic	0.6642	pathogenic	0.144	Stabilizing	0.998	D	0.653	prob.neutral	N	0.507395016	None	None	I
K/P	0.2807	likely_benign	0.2872	benign	0.102	Stabilizing	0.998	D	0.627	neutral	None	None	None	None	I
K/Q	0.2052	likely_benign	0.2052	benign	-0.172	Destabilizing	0.998	D	0.679	prob.neutral	N	0.512243476	None	None	I
K/R	0.092	likely_benign	0.0905	benign	-0.069	Destabilizing	0.992	D	0.615	neutral	N	0.418082521	None	None	I
K/S	0.5671	likely_pathogenic	0.592	pathogenic	-0.463	Destabilizing	0.994	D	0.657	prob.neutral	None	None	None	None	I
K/T	0.2289	likely_benign	0.2558	benign	-0.3	Destabilizing	0.993	D	0.595	neutral	N	0.462526732	None	None	I
K/V	0.2121	likely_benign	0.2385	benign	0.102	Stabilizing	0.931	D	0.507	neutral	None	None	None	None	I
K/W	0.8666	likely_pathogenic	0.8885	pathogenic	-0.432	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
K/Y	0.713	likely_pathogenic	0.7401	pathogenic	-0.067	Destabilizing	0.998	D	0.794	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.