TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13765	41518;41519;41520	chr2:178636434;178636433;178636432	chr2:179501161;179501160;179501159
N2AB	12124	36595;36596;36597	chr2:178636434;178636433;178636432	chr2:179501161;179501160;179501159
N2A	11197	33814;33815;33816	chr2:178636434;178636433;178636432	chr2:179501161;179501160;179501159
N2B	4700	14323;14324;14325	chr2:178636434;178636433;178636432	chr2:179501161;179501160;179501159
Novex-1	4825	14698;14699;14700	chr2:178636434;178636433;178636432	chr2:179501161;179501160;179501159
Novex-2	4892	14899;14900;14901	chr2:178636434;178636433;178636432	chr2:179501161;179501160;179501159
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-87
• Domain position: 82
• Structural Position: 164
• Q(SASA): 0.6084
• 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	rs1376605407	0.025	0.996	N	0.519	0.432	0.435152311215	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
K/E	rs1376605407	0.025	0.996	N	0.519	0.432	0.435152311215	gnomAD-4.0.0	2.05607E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70149E-05	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	0.9335	likely_pathogenic	0.9589	pathogenic	0.07	Stabilizing	0.998	D	0.547	neutral	None	None	None	None	I
K/C	0.9905	likely_pathogenic	0.9923	pathogenic	-0.322	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/D	0.9779	likely_pathogenic	0.9878	pathogenic	-0.037	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	I
K/E	0.8658	likely_pathogenic	0.9251	pathogenic	-0.038	Destabilizing	0.996	D	0.519	neutral	N	0.456187271	None	None	I
K/F	0.9942	likely_pathogenic	0.9965	pathogenic	-0.201	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
K/G	0.9513	likely_pathogenic	0.9635	pathogenic	-0.097	Destabilizing	0.997	D	0.586	neutral	None	None	None	None	I
K/H	0.8645	likely_pathogenic	0.8981	pathogenic	-0.284	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	I
K/I	0.9346	likely_pathogenic	0.9602	pathogenic	0.423	Stabilizing	1.0	D	0.645	neutral	N	0.513657448	None	None	I
K/L	0.9256	likely_pathogenic	0.9522	pathogenic	0.423	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	I
K/M	0.8809	likely_pathogenic	0.9185	pathogenic	0.09	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	I
K/N	0.9552	likely_pathogenic	0.9731	pathogenic	0.127	Stabilizing	0.884	D	0.327	neutral	N	0.485973397	None	None	I
K/P	0.9946	likely_pathogenic	0.9964	pathogenic	0.331	Stabilizing	1.0	D	0.574	neutral	None	None	None	None	I
K/Q	0.6119	likely_pathogenic	0.7089	pathogenic	-0.014	Destabilizing	0.999	D	0.634	neutral	N	0.494703994	None	None	I
K/R	0.1737	likely_benign	0.1879	benign	-0.057	Destabilizing	0.998	D	0.555	neutral	N	0.492911842	None	None	I
K/S	0.9552	likely_pathogenic	0.9728	pathogenic	-0.292	Destabilizing	0.997	D	0.519	neutral	None	None	None	None	I
K/T	0.824	likely_pathogenic	0.885	pathogenic	-0.158	Destabilizing	0.999	D	0.565	neutral	N	0.51019007	None	None	I
K/V	0.8983	likely_pathogenic	0.9322	pathogenic	0.331	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	I
K/W	0.9892	likely_pathogenic	0.9925	pathogenic	-0.273	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
K/Y	0.9793	likely_pathogenic	0.985	pathogenic	0.09	Stabilizing	1.0	D	0.65	neutral	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.