TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28573	85942;85943;85944	chr2:178560415;178560414;178560413	chr2:179425142;179425141;179425140
N2AB	26932	81019;81020;81021	chr2:178560415;178560414;178560413	chr2:179425142;179425141;179425140
N2A	26005	78238;78239;78240	chr2:178560415;178560414;178560413	chr2:179425142;179425141;179425140
N2B	19508	58747;58748;58749	chr2:178560415;178560414;178560413	chr2:179425142;179425141;179425140
Novex-1	19633	59122;59123;59124	chr2:178560415;178560414;178560413	chr2:179425142;179425141;179425140
Novex-2	19700	59323;59324;59325	chr2:178560415;178560414;178560413	chr2:179425142;179425141;179425140
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: Fn3-96
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6318
• 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
R/K	None	None	0.656	N	0.567	0.158	0.3085936734	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0248E-05

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	0.5095	ambiguous	0.4767	ambiguous	-0.256	Destabilizing	0.559	D	0.533	neutral	None	None	None	None	N
R/C	0.1915	likely_benign	0.1751	benign	-0.592	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
R/D	0.8311	likely_pathogenic	0.8174	pathogenic	-0.592	Destabilizing	0.956	D	0.663	neutral	None	None	None	None	N
R/E	0.5034	ambiguous	0.4692	ambiguous	-0.469	Destabilizing	0.86	D	0.561	neutral	None	None	None	None	N
R/F	0.595	likely_pathogenic	0.5785	pathogenic	-0.322	Destabilizing	0.956	D	0.717	prob.delet.	None	None	None	None	N
R/G	0.4255	ambiguous	0.3819	ambiguous	-0.485	Destabilizing	0.698	D	0.593	neutral	N	0.467405539	None	None	N
R/H	0.1094	likely_benign	0.107	benign	-1.186	Destabilizing	0.993	D	0.599	neutral	None	None	None	None	N
R/I	0.4185	ambiguous	0.3979	ambiguous	0.338	Stabilizing	0.89	D	0.658	neutral	N	0.49661261	None	None	N
R/K	0.1415	likely_benign	0.1362	benign	-0.315	Destabilizing	0.656	D	0.567	neutral	N	0.475997461	None	None	N
R/L	0.3103	likely_benign	0.2798	benign	0.338	Stabilizing	0.019	N	0.401	neutral	None	None	None	None	N
R/M	0.4201	ambiguous	0.3953	ambiguous	-0.346	Destabilizing	0.956	D	0.681	prob.neutral	None	None	None	None	N
R/N	0.7438	likely_pathogenic	0.7293	pathogenic	-0.458	Destabilizing	0.86	D	0.585	neutral	None	None	None	None	N
R/P	0.3971	ambiguous	0.356	ambiguous	0.159	Stabilizing	0.978	D	0.715	prob.delet.	None	None	None	None	N
R/Q	0.1389	likely_benign	0.1271	benign	-0.368	Destabilizing	0.978	D	0.638	neutral	None	None	None	None	N
R/S	0.623	likely_pathogenic	0.5916	pathogenic	-0.683	Destabilizing	0.058	N	0.275	neutral	N	0.465822149	None	None	N
R/T	0.4854	ambiguous	0.4518	ambiguous	-0.399	Destabilizing	0.698	D	0.574	neutral	N	0.473481925	None	None	N
R/V	0.4916	ambiguous	0.4657	ambiguous	0.159	Stabilizing	0.754	D	0.648	neutral	None	None	None	None	N
R/W	0.1938	likely_benign	0.1783	benign	-0.412	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
R/Y	0.4001	ambiguous	0.3925	ambiguous	-0.045	Destabilizing	0.978	D	0.705	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.