TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4703	14332;14333;14334	chr2:178738346;178738345;178738344	chr2:179603073;179603072;179603071
N2AB	4386	13381;13382;13383	chr2:178738346;178738345;178738344	chr2:179603073;179603072;179603071
N2A	3459	10600;10601;10602	chr2:178738346;178738345;178738344	chr2:179603073;179603072;179603071
N2B	4340	13243;13244;13245	chr2:178738346;178738345;178738344	chr2:179603073;179603072;179603071
Novex-1	4465	13618;13619;13620	chr2:178738346;178738345;178738344	chr2:179603073;179603072;179603071
Novex-2	4532	13819;13820;13821	chr2:178738346;178738345;178738344	chr2:179603073;179603072;179603071
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-30
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5476
• 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/Q	rs1479181903	0.064	0.117	N	0.318	0.133	0.12205267543	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/Q	rs1479181903	0.064	0.117	N	0.318	0.133	0.12205267543	gnomAD-4.0.0	1.59553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86763E-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	0.3736	ambiguous	0.4257	ambiguous	-0.231	Destabilizing	0.067	N	0.321	neutral	None	None	None	None	N
K/C	0.65	likely_pathogenic	0.7099	pathogenic	-0.479	Destabilizing	0.935	D	0.314	neutral	None	None	None	None	N
K/D	0.7243	likely_pathogenic	0.7562	pathogenic	-0.098	Destabilizing	0.149	N	0.368	neutral	None	None	None	None	N
K/E	0.21	likely_benign	0.2399	benign	-0.02	Destabilizing	0.027	N	0.271	neutral	N	0.436051124	None	None	N
K/F	0.7385	likely_pathogenic	0.7745	pathogenic	0.016	Stabilizing	0.555	D	0.363	neutral	None	None	None	None	N
K/G	0.4266	ambiguous	0.4784	ambiguous	-0.55	Destabilizing	0.149	N	0.36	neutral	None	None	None	None	N
K/H	0.3207	likely_benign	0.3468	ambiguous	-0.784	Destabilizing	0.555	D	0.273	neutral	None	None	None	None	N
K/I	0.2851	likely_benign	0.3315	benign	0.567	Stabilizing	0.002	N	0.241	neutral	None	None	None	None	N
K/L	0.2949	likely_benign	0.3309	benign	0.567	Stabilizing	0.035	N	0.317	neutral	None	None	None	None	N
K/M	0.2405	likely_benign	0.2647	benign	0.223	Stabilizing	0.484	N	0.274	neutral	N	0.443554199	None	None	N
K/N	0.5032	ambiguous	0.5365	ambiguous	-0.357	Destabilizing	0.117	N	0.258	neutral	N	0.450160553	None	None	N
K/P	0.8634	likely_pathogenic	0.8761	pathogenic	0.331	Stabilizing	0.555	D	0.365	neutral	None	None	None	None	N
K/Q	0.123	likely_benign	0.1397	benign	-0.424	Destabilizing	0.117	N	0.318	neutral	N	0.444937374	None	None	N
K/R	0.0648	likely_benign	0.0701	benign	-0.494	Destabilizing	None	N	0.084	neutral	N	0.377019657	None	None	N
K/S	0.4441	ambiguous	0.4884	ambiguous	-0.879	Destabilizing	0.149	N	0.237	neutral	None	None	None	None	N
K/T	0.1772	likely_benign	0.1962	benign	-0.621	Destabilizing	0.117	N	0.356	neutral	N	0.399809287	None	None	N
K/V	0.2837	likely_benign	0.3247	benign	0.331	Stabilizing	0.035	N	0.315	neutral	None	None	None	None	N
K/W	0.6429	likely_pathogenic	0.6991	pathogenic	0.067	Stabilizing	0.935	D	0.354	neutral	None	None	None	None	N
K/Y	0.6103	likely_pathogenic	0.6537	pathogenic	0.349	Stabilizing	0.555	D	0.341	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.