TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9674	29245;29246;29247	chr2:178707547;178707546;178707545	chr2:179572274;179572273;179572272
N2AB	9357	28294;28295;28296	chr2:178707547;178707546;178707545	chr2:179572274;179572273;179572272
N2A	8430	25513;25514;25515	chr2:178707547;178707546;178707545	chr2:179572274;179572273;179572272
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-82
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.474
• 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	None	None	0.968	None	0.631	0.248	0.292423486923	gnomAD-4.0.0	6.84432E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09765E-06	0	1.65678E-05

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	0.5235	ambiguous	0.3807	ambiguous	-0.187	Destabilizing	0.702	D	0.614	neutral	None	None	None	None	N
K/C	0.8539	likely_pathogenic	0.7946	pathogenic	-0.25	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
K/D	0.8649	likely_pathogenic	0.7669	pathogenic	0.197	Stabilizing	0.976	D	0.683	prob.neutral	None	None	None	None	N
K/E	0.461	ambiguous	0.3036	benign	0.215	Stabilizing	0.896	D	0.609	neutral	None	None	None	None	N
K/F	0.8804	likely_pathogenic	0.7979	pathogenic	-0.331	Destabilizing	0.988	D	0.757	deleterious	None	None	None	None	N
K/G	0.6768	likely_pathogenic	0.5283	ambiguous	-0.423	Destabilizing	0.919	D	0.676	prob.neutral	None	None	None	None	N
K/H	0.4515	ambiguous	0.3915	ambiguous	-0.796	Destabilizing	0.997	D	0.687	prob.neutral	None	None	None	None	N
K/I	0.5596	ambiguous	0.4164	ambiguous	0.365	Stabilizing	0.968	D	0.752	deleterious	None	None	None	None	N
K/L	0.5831	likely_pathogenic	0.4398	ambiguous	0.365	Stabilizing	0.851	D	0.68	prob.neutral	None	None	None	None	N
K/M	0.4497	ambiguous	0.3276	benign	0.321	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
K/N	0.6765	likely_pathogenic	0.5332	ambiguous	0.182	Stabilizing	0.896	D	0.599	neutral	None	None	None	None	N
K/P	0.8786	likely_pathogenic	0.7669	pathogenic	0.21	Stabilizing	0.988	D	0.706	prob.neutral	None	None	None	None	N
K/Q	0.2309	likely_benign	0.1811	benign	-0.045	Destabilizing	0.968	D	0.631	neutral	None	None	None	None	N
K/R	0.088	likely_benign	0.0829	benign	-0.112	Destabilizing	0.059	N	0.423	neutral	None	None	None	None	N
K/S	0.5779	likely_pathogenic	0.4372	ambiguous	-0.426	Destabilizing	0.307	N	0.423	neutral	None	None	None	None	N
K/T	0.2837	likely_benign	0.1894	benign	-0.245	Destabilizing	0.103	N	0.442	neutral	None	None	None	None	N
K/V	0.4703	ambiguous	0.3637	ambiguous	0.21	Stabilizing	0.952	D	0.711	prob.delet.	None	None	None	None	N
K/W	0.8743	likely_pathogenic	0.7925	pathogenic	-0.251	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/Y	0.7874	likely_pathogenic	0.6948	pathogenic	0.092	Stabilizing	0.996	D	0.748	deleterious	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.