TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23613	71062;71063;71064	chr2:178575295;178575294;178575293	chr2:179440022;179440021;179440020
N2AB	21972	66139;66140;66141	chr2:178575295;178575294;178575293	chr2:179440022;179440021;179440020
N2A	21045	63358;63359;63360	chr2:178575295;178575294;178575293	chr2:179440022;179440021;179440020
N2B	14548	43867;43868;43869	chr2:178575295;178575294;178575293	chr2:179440022;179440021;179440020
Novex-1	14673	44242;44243;44244	chr2:178575295;178575294;178575293	chr2:179440022;179440021;179440020
Novex-2	14740	44443;44444;44445	chr2:178575295;178575294;178575293	chr2:179440022;179440021;179440020
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-59
• Domain position: 82
• Structural Position: 117
• Q(SASA): 0.7313
• 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
R/K	rs1383287130	None	0.795	N	0.475	0.081	0.168933306366	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/K	rs1383287130	None	0.795	N	0.475	0.081	0.168933306366	gnomAD-4.0.0	6.57454E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47054E-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
R/A	0.6307	likely_pathogenic	0.733	pathogenic	-0.395	Destabilizing	0.717	D	0.545	neutral	None	None	None	None	I
R/C	0.2918	likely_benign	0.3856	ambiguous	-0.465	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	I
R/D	0.8581	likely_pathogenic	0.9048	pathogenic	0.035	Stabilizing	0.978	D	0.667	neutral	None	None	None	None	I
R/E	0.5354	ambiguous	0.6323	pathogenic	0.113	Stabilizing	0.926	D	0.586	neutral	None	None	None	None	I
R/F	0.6668	likely_pathogenic	0.748	pathogenic	-0.555	Destabilizing	0.956	D	0.686	prob.neutral	None	None	None	None	I
R/G	0.5711	likely_pathogenic	0.6755	pathogenic	-0.618	Destabilizing	0.904	D	0.648	neutral	N	0.464982321	None	None	I
R/H	0.1749	likely_benign	0.2373	benign	-1.0	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	I
R/I	0.3664	ambiguous	0.4567	ambiguous	0.17	Stabilizing	0.89	D	0.631	neutral	N	0.445671767	None	None	I
R/K	0.1391	likely_benign	0.1928	benign	-0.36	Destabilizing	0.795	D	0.475	neutral	N	0.428952876	None	None	I
R/L	0.349	ambiguous	0.4427	ambiguous	0.17	Stabilizing	0.019	N	0.457	neutral	None	None	None	None	I
R/M	0.4216	ambiguous	0.5433	ambiguous	-0.154	Destabilizing	0.956	D	0.641	neutral	None	None	None	None	I
R/N	0.749	likely_pathogenic	0.8269	pathogenic	0.005	Stabilizing	0.978	D	0.592	neutral	None	None	None	None	I
R/P	0.6911	likely_pathogenic	0.7704	pathogenic	0.003	Stabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	I
R/Q	0.1558	likely_benign	0.2177	benign	-0.172	Destabilizing	0.993	D	0.623	neutral	None	None	None	None	I
R/S	0.73	likely_pathogenic	0.8157	pathogenic	-0.587	Destabilizing	0.698	D	0.58	neutral	N	0.464449529	None	None	I
R/T	0.4108	ambiguous	0.601	pathogenic	-0.358	Destabilizing	0.058	N	0.383	neutral	N	0.470452781	None	None	I
R/V	0.4549	ambiguous	0.5679	pathogenic	0.003	Stabilizing	0.754	D	0.627	neutral	None	None	None	None	I
R/W	0.2943	likely_benign	0.3601	ambiguous	-0.441	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	I
R/Y	0.4739	ambiguous	0.5715	pathogenic	-0.066	Destabilizing	0.978	D	0.691	prob.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.