TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28282	85069;85070;85071	chr2:178561288;178561287;178561286	chr2:179426015;179426014;179426013
N2AB	26641	80146;80147;80148	chr2:178561288;178561287;178561286	chr2:179426015;179426014;179426013
N2A	25714	77365;77366;77367	chr2:178561288;178561287;178561286	chr2:179426015;179426014;179426013
N2B	19217	57874;57875;57876	chr2:178561288;178561287;178561286	chr2:179426015;179426014;179426013
Novex-1	19342	58249;58250;58251	chr2:178561288;178561287;178561286	chr2:179426015;179426014;179426013
Novex-2	19409	58450;58451;58452	chr2:178561288;178561287;178561286	chr2:179426015;179426014;179426013
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-94
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2656
• 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
A/P	None	None	0.939	N	0.651	0.44	0.379193981924	gnomAD-4.0.0	6.84212E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99446E-07	0	0
A/T	rs1703576117	None	0.521	N	0.591	0.121	0.259761712551	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
A/T	rs1703576117	None	0.521	N	0.591	0.121	0.259761712551	gnomAD-4.0.0	1.23941E-06	None	None	None	None	I	None	1.33486E-05	1.66711E-05	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
A/C	0.4871	ambiguous	0.5138	ambiguous	-0.738	Destabilizing	0.996	D	0.623	neutral	None	None	None	None	I
A/D	0.78	likely_pathogenic	0.7417	pathogenic	-0.998	Destabilizing	0.884	D	0.677	prob.neutral	N	0.470216696	None	None	I
A/E	0.6854	likely_pathogenic	0.6557	pathogenic	-1.154	Destabilizing	0.742	D	0.639	neutral	None	None	None	None	I
A/F	0.4446	ambiguous	0.4494	ambiguous	-1.25	Destabilizing	0.953	D	0.669	neutral	None	None	None	None	I
A/G	0.264	likely_benign	0.2435	benign	-0.642	Destabilizing	0.521	D	0.585	neutral	N	0.491750773	None	None	I
A/H	0.6865	likely_pathogenic	0.6707	pathogenic	-0.66	Destabilizing	0.996	D	0.646	neutral	None	None	None	None	I
A/I	0.5345	ambiguous	0.5777	pathogenic	-0.561	Destabilizing	0.037	N	0.456	neutral	None	None	None	None	I
A/K	0.8717	likely_pathogenic	0.8553	pathogenic	-0.789	Destabilizing	0.91	D	0.641	neutral	None	None	None	None	I
A/L	0.3557	ambiguous	0.3696	ambiguous	-0.561	Destabilizing	0.373	N	0.563	neutral	None	None	None	None	I
A/M	0.3808	ambiguous	0.3965	ambiguous	-0.265	Destabilizing	0.953	D	0.645	neutral	None	None	None	None	I
A/N	0.5773	likely_pathogenic	0.5625	ambiguous	-0.451	Destabilizing	0.91	D	0.657	neutral	None	None	None	None	I
A/P	0.9587	likely_pathogenic	0.9507	pathogenic	-0.53	Destabilizing	0.939	D	0.651	neutral	N	0.48861412	None	None	I
A/Q	0.6211	likely_pathogenic	0.5985	pathogenic	-0.819	Destabilizing	0.91	D	0.65	neutral	None	None	None	None	I
A/R	0.7849	likely_pathogenic	0.755	pathogenic	-0.227	Destabilizing	0.91	D	0.65	neutral	None	None	None	None	I
A/S	0.1011	likely_benign	0.0996	benign	-0.642	Destabilizing	0.028	N	0.439	neutral	N	0.371062152	None	None	I
A/T	0.1721	likely_benign	0.1785	benign	-0.731	Destabilizing	0.521	D	0.591	neutral	N	0.508437953	None	None	I
A/V	0.2698	likely_benign	0.3036	benign	-0.53	Destabilizing	0.012	N	0.335	neutral	N	0.505128289	None	None	I
A/W	0.8575	likely_pathogenic	0.8537	pathogenic	-1.369	Destabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	I
A/Y	0.6408	likely_pathogenic	0.6369	pathogenic	-1.023	Destabilizing	0.984	D	0.67	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.