TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30770	92533;92534;92535	chr2:178549318;178549317;178549316	chr2:179414045;179414044;179414043
N2AB	29129	87610;87611;87612	chr2:178549318;178549317;178549316	chr2:179414045;179414044;179414043
N2A	28202	84829;84830;84831	chr2:178549318;178549317;178549316	chr2:179414045;179414044;179414043
N2B	21705	65338;65339;65340	chr2:178549318;178549317;178549316	chr2:179414045;179414044;179414043
Novex-1	21830	65713;65714;65715	chr2:178549318;178549317;178549316	chr2:179414045;179414044;179414043
Novex-2	21897	65914;65915;65916	chr2:178549318;178549317;178549316	chr2:179414045;179414044;179414043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-112
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1082
• 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
I/T	None	None	None	N	0.301	0.063	0.331876078066	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
I/A	0.1544	likely_benign	0.1582	benign	-0.561	Destabilizing	0.011	N	0.41	neutral	None	None	None	None	N
I/C	0.3862	ambiguous	0.4095	ambiguous	-0.958	Destabilizing	0.667	D	0.542	neutral	None	None	None	None	N
I/D	0.5046	ambiguous	0.5259	ambiguous	-0.262	Destabilizing	0.104	N	0.522	neutral	None	None	None	None	N
I/E	0.5208	ambiguous	0.5488	ambiguous	-0.346	Destabilizing	0.104	N	0.529	neutral	None	None	None	None	N
I/F	0.115	likely_benign	0.1261	benign	-0.702	Destabilizing	0.301	N	0.512	neutral	N	0.464551103	None	None	N
I/G	0.3045	likely_benign	0.3131	benign	-0.644	Destabilizing	0.055	N	0.507	neutral	None	None	None	None	N
I/H	0.2968	likely_benign	0.3295	benign	0.005	Stabilizing	0.667	D	0.587	neutral	None	None	None	None	N
I/K	0.3854	ambiguous	0.407	ambiguous	-0.468	Destabilizing	0.055	N	0.525	neutral	None	None	None	None	N
I/L	0.0831	likely_benign	0.0895	benign	-0.452	Destabilizing	0.019	N	0.29	neutral	N	0.427206223	None	None	N
I/M	0.0814	likely_benign	0.0904	benign	-0.755	Destabilizing	0.602	D	0.527	neutral	N	0.446138701	None	None	N
I/N	0.1133	likely_benign	0.116	benign	-0.399	Destabilizing	0.042	N	0.531	neutral	N	0.424779207	None	None	N
I/P	0.295	likely_benign	0.3289	benign	-0.463	Destabilizing	0.364	N	0.573	neutral	None	None	None	None	N
I/Q	0.3017	likely_benign	0.3328	benign	-0.543	Destabilizing	0.22	N	0.616	neutral	None	None	None	None	N
I/R	0.3038	likely_benign	0.3189	benign	-0.034	Destabilizing	0.22	N	0.607	neutral	None	None	None	None	N
I/S	0.1124	likely_benign	0.1105	benign	-0.779	Destabilizing	None	N	0.319	neutral	N	0.387338326	None	None	N
I/T	0.1172	likely_benign	0.1233	benign	-0.767	Destabilizing	None	N	0.301	neutral	N	0.426414003	None	None	N
I/V	0.077	likely_benign	0.0803	benign	-0.463	Destabilizing	0.019	N	0.299	neutral	N	0.431881324	None	None	N
I/W	0.6028	likely_pathogenic	0.6327	pathogenic	-0.71	Destabilizing	0.958	D	0.573	neutral	None	None	None	None	N
I/Y	0.3235	likely_benign	0.3232	benign	-0.509	Destabilizing	0.667	D	0.587	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.