TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17189	51790;51791;51792	chr2:178609858;178609857;178609856	chr2:179474585;179474584;179474583
N2AB	15548	46867;46868;46869	chr2:178609858;178609857;178609856	chr2:179474585;179474584;179474583
N2A	14621	44086;44087;44088	chr2:178609858;178609857;178609856	chr2:179474585;179474584;179474583
N2B	8124	24595;24596;24597	chr2:178609858;178609857;178609856	chr2:179474585;179474584;179474583
Novex-1	8249	24970;24971;24972	chr2:178609858;178609857;178609856	chr2:179474585;179474584;179474583
Novex-2	8316	25171;25172;25173	chr2:178609858;178609857;178609856	chr2:179474585;179474584;179474583
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-13
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.5831
• 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/E	rs727503618	0.247	0.999	N	0.697	0.421	0.399449838166	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-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
K/A	0.4291	ambiguous	0.3709	ambiguous	0.021	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/C	0.849	likely_pathogenic	0.7963	pathogenic	-0.152	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/D	0.7517	likely_pathogenic	0.6686	pathogenic	0.081	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/E	0.2904	likely_benign	0.2379	benign	0.099	Stabilizing	0.999	D	0.697	prob.neutral	N	0.480096559	None	None	N
K/F	0.8929	likely_pathogenic	0.8252	pathogenic	-0.106	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/G	0.6542	likely_pathogenic	0.5718	pathogenic	-0.199	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
K/H	0.4882	ambiguous	0.4259	ambiguous	-0.47	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
K/I	0.4695	ambiguous	0.3844	ambiguous	0.528	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/L	0.527	ambiguous	0.4425	ambiguous	0.528	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
K/M	0.41	ambiguous	0.3432	ambiguous	0.25	Stabilizing	1.0	D	0.609	neutral	N	0.482284244	None	None	N
K/N	0.6574	likely_pathogenic	0.5704	pathogenic	0.259	Stabilizing	1.0	D	0.699	prob.neutral	N	0.521868611	None	None	N
K/P	0.7316	likely_pathogenic	0.6698	pathogenic	0.388	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/Q	0.2146	likely_benign	0.1895	benign	0.105	Stabilizing	1.0	D	0.687	prob.neutral	N	0.469660491	None	None	N
K/R	0.0912	likely_benign	0.0879	benign	-0.054	Destabilizing	0.999	D	0.608	neutral	N	0.521521894	None	None	N
K/S	0.5874	likely_pathogenic	0.5088	ambiguous	-0.222	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
K/T	0.336	likely_benign	0.2776	benign	-0.05	Destabilizing	1.0	D	0.683	prob.neutral	N	0.4843103	None	None	N
K/V	0.4041	ambiguous	0.3392	benign	0.388	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
K/W	0.8849	likely_pathogenic	0.8222	pathogenic	-0.119	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/Y	0.8088	likely_pathogenic	0.721	pathogenic	0.225	Stabilizing	1.0	D	0.666	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.