TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30513	91762;91763;91764	chr2:178550994;178550993;178550992	chr2:179415721;179415720;179415719
N2AB	28872	86839;86840;86841	chr2:178550994;178550993;178550992	chr2:179415721;179415720;179415719
N2A	27945	84058;84059;84060	chr2:178550994;178550993;178550992	chr2:179415721;179415720;179415719
N2B	21448	64567;64568;64569	chr2:178550994;178550993;178550992	chr2:179415721;179415720;179415719
Novex-1	21573	64942;64943;64944	chr2:178550994;178550993;178550992	chr2:179415721;179415720;179415719
Novex-2	21640	65143;65144;65145	chr2:178550994;178550993;178550992	chr2:179415721;179415720;179415719
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-110
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.3432
• 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
G/D	rs748076186	0.422	1.0	N	0.735	0.321	0.265010934533	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.11982E-04	None	0	None	0	8.93E-06	0
G/D	rs748076186	0.422	1.0	N	0.735	0.321	0.265010934533	gnomAD-4.0.0	6.84536E-06	None	None	None	None	N	None	0	0	None	0	5.04923E-05	None	0	0	7.19747E-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
G/A	0.434	ambiguous	0.5453	ambiguous	-0.33	Destabilizing	0.999	D	0.719	prob.delet.	N	0.473165013	None	None	N
G/C	0.7253	likely_pathogenic	0.7982	pathogenic	-0.895	Destabilizing	1.0	D	0.595	neutral	N	0.476174042	None	None	N
G/D	0.7624	likely_pathogenic	0.8561	pathogenic	-0.093	Destabilizing	1.0	D	0.735	deleterious	N	0.424469776	None	None	N
G/E	0.7775	likely_pathogenic	0.8533	pathogenic	-0.201	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
G/F	0.9507	likely_pathogenic	0.9726	pathogenic	-0.75	Destabilizing	1.0	D	0.674	prob.neutral	None	None	None	None	N
G/H	0.8808	likely_pathogenic	0.9214	pathogenic	-0.602	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
G/I	0.8954	likely_pathogenic	0.9433	pathogenic	-0.229	Destabilizing	1.0	D	0.705	prob.delet.	None	None	None	None	N
G/K	0.8811	likely_pathogenic	0.9209	pathogenic	-0.766	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/L	0.8934	likely_pathogenic	0.9347	pathogenic	-0.229	Destabilizing	1.0	D	0.727	deleterious	None	None	None	None	N
G/M	0.912	likely_pathogenic	0.9469	pathogenic	-0.386	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
G/N	0.6922	likely_pathogenic	0.7911	pathogenic	-0.513	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
G/P	0.9546	likely_pathogenic	0.9757	pathogenic	-0.224	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
G/Q	0.7816	likely_pathogenic	0.842	pathogenic	-0.689	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
G/R	0.7711	likely_pathogenic	0.845	pathogenic	-0.463	Destabilizing	1.0	D	0.732	deleterious	N	0.499812896	None	None	N
G/S	0.2716	likely_benign	0.3616	ambiguous	-0.807	Destabilizing	1.0	D	0.724	deleterious	N	0.492481492	None	None	N
G/T	0.6457	likely_pathogenic	0.7542	pathogenic	-0.821	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
G/V	0.7994	likely_pathogenic	0.8853	pathogenic	-0.224	Destabilizing	1.0	D	0.738	deleterious	N	0.478205473	None	None	N
G/W	0.931	likely_pathogenic	0.9611	pathogenic	-0.974	Destabilizing	1.0	D	0.559	neutral	None	None	None	None	N
G/Y	0.9197	likely_pathogenic	0.9549	pathogenic	-0.583	Destabilizing	1.0	D	0.679	prob.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.