TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30201	90826;90827;90828	chr2:178552299;178552298;178552297	chr2:179417026;179417025;179417024
N2AB	28560	85903;85904;85905	chr2:178552299;178552298;178552297	chr2:179417026;179417025;179417024
N2A	27633	83122;83123;83124	chr2:178552299;178552298;178552297	chr2:179417026;179417025;179417024
N2B	21136	63631;63632;63633	chr2:178552299;178552298;178552297	chr2:179417026;179417025;179417024
Novex-1	21261	64006;64007;64008	chr2:178552299;178552298;178552297	chr2:179417026;179417025;179417024
Novex-2	21328	64207;64208;64209	chr2:178552299;178552298;178552297	chr2:179417026;179417025;179417024
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-148
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.7025
• 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/N	rs931505367	None	0.998	N	0.663	0.334	0.292062946507	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs931505367	None	0.998	N	0.663	0.334	0.292062946507	gnomAD-4.0.0	1.31435E-05	None	None	None	None	N	None	4.82509E-05	0	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	0.2989	likely_benign	0.3131	benign	-0.475	Destabilizing	0.992	D	0.638	neutral	None	None	None	None	N
K/C	0.5478	ambiguous	0.5905	pathogenic	-0.584	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
K/D	0.4857	ambiguous	0.5014	ambiguous	-0.196	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
K/E	0.1623	likely_benign	0.1702	benign	-0.123	Destabilizing	0.978	D	0.613	neutral	N	0.506603662	None	None	N
K/F	0.6449	likely_pathogenic	0.6633	pathogenic	-0.421	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/G	0.4873	ambiguous	0.5175	ambiguous	-0.797	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
K/H	0.2403	likely_benign	0.2466	benign	-1.24	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
K/I	0.1925	likely_benign	0.205	benign	0.338	Stabilizing	0.999	D	0.72	prob.delet.	D	0.527480366	None	None	N
K/L	0.2733	likely_benign	0.2938	benign	0.338	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	N
K/M	0.1676	likely_benign	0.1774	benign	0.355	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/N	0.2825	likely_benign	0.2935	benign	-0.321	Destabilizing	0.998	D	0.663	neutral	N	0.514551141	None	None	N
K/P	0.6879	likely_pathogenic	0.6823	pathogenic	0.098	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/Q	0.1102	likely_benign	0.1157	benign	-0.521	Destabilizing	0.775	D	0.322	neutral	N	0.5013712	None	None	N
K/R	0.081	likely_benign	0.0837	benign	-0.47	Destabilizing	0.989	D	0.586	neutral	N	0.512492271	None	None	N
K/S	0.3145	likely_benign	0.338	benign	-0.979	Destabilizing	0.992	D	0.626	neutral	None	None	None	None	N
K/T	0.1177	likely_benign	0.124	benign	-0.715	Destabilizing	0.998	D	0.691	prob.neutral	N	0.496965458	None	None	N
K/V	0.1925	likely_benign	0.2097	benign	0.098	Stabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
K/W	0.7186	likely_pathogenic	0.7292	pathogenic	-0.289	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/Y	0.5034	ambiguous	0.5189	ambiguous	0.054	Stabilizing	1.0	D	0.707	prob.neutral	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.