TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24270	73033;73034;73035	chr2:178573324;178573323;178573322	chr2:179438051;179438050;179438049
N2AB	22629	68110;68111;68112	chr2:178573324;178573323;178573322	chr2:179438051;179438050;179438049
N2A	21702	65329;65330;65331	chr2:178573324;178573323;178573322	chr2:179438051;179438050;179438049
N2B	15205	45838;45839;45840	chr2:178573324;178573323;178573322	chr2:179438051;179438050;179438049
Novex-1	15330	46213;46214;46215	chr2:178573324;178573323;178573322	chr2:179438051;179438050;179438049
Novex-2	15397	46414;46415;46416	chr2:178573324;178573323;178573322	chr2:179438051;179438050;179438049
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-64
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.1869
• 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	0.062	N	0.349	0.226	0.532696708436	gnomAD-4.0.0	7.08956E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.31007E-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	0.4234	ambiguous	0.3792	ambiguous	-1.408	Destabilizing	0.035	N	0.344	neutral	None	None	None	None	N
I/C	0.6195	likely_pathogenic	0.5808	pathogenic	-0.804	Destabilizing	0.824	D	0.345	neutral	None	None	None	None	N
I/D	0.8948	likely_pathogenic	0.8389	pathogenic	-0.907	Destabilizing	0.555	D	0.413	neutral	None	None	None	None	N
I/E	0.8059	likely_pathogenic	0.7359	pathogenic	-0.925	Destabilizing	0.555	D	0.405	neutral	None	None	None	None	N
I/F	0.2066	likely_benign	0.1887	benign	-0.964	Destabilizing	0.317	N	0.386	neutral	N	0.479461841	None	None	N
I/G	0.6099	likely_pathogenic	0.5398	ambiguous	-1.695	Destabilizing	0.262	N	0.342	neutral	None	None	None	None	N
I/H	0.6512	likely_pathogenic	0.5809	pathogenic	-0.851	Destabilizing	0.935	D	0.43	neutral	None	None	None	None	N
I/K	0.7248	likely_pathogenic	0.6261	pathogenic	-0.998	Destabilizing	0.555	D	0.403	neutral	None	None	None	None	N
I/L	0.1356	likely_benign	0.1278	benign	-0.711	Destabilizing	0.005	N	0.223	neutral	N	0.445194551	None	None	N
I/M	0.0938	likely_benign	0.0899	benign	-0.579	Destabilizing	0.317	N	0.435	neutral	N	0.468668844	None	None	N
I/N	0.3092	likely_benign	0.2729	benign	-0.799	Destabilizing	0.741	D	0.441	neutral	N	0.490118765	None	None	N
I/P	0.9547	likely_pathogenic	0.9347	pathogenic	-0.912	Destabilizing	0.555	D	0.425	neutral	None	None	None	None	N
I/Q	0.526	ambiguous	0.4568	ambiguous	-0.998	Destabilizing	0.791	D	0.438	neutral	None	None	None	None	N
I/R	0.6398	likely_pathogenic	0.5369	ambiguous	-0.357	Destabilizing	0.555	D	0.435	neutral	None	None	None	None	N
I/S	0.3476	ambiguous	0.3167	benign	-1.343	Destabilizing	0.117	N	0.312	neutral	N	0.467628694	None	None	N
I/T	0.2493	likely_benign	0.2186	benign	-1.253	Destabilizing	0.062	N	0.349	neutral	N	0.380548427	None	None	N
I/V	0.0663	likely_benign	0.0625	benign	-0.912	Destabilizing	None	N	0.142	neutral	N	0.371678228	None	None	N
I/W	0.8428	likely_pathogenic	0.7925	pathogenic	-1.019	Destabilizing	0.935	D	0.479	neutral	None	None	None	None	N
I/Y	0.5678	likely_pathogenic	0.5205	ambiguous	-0.809	Destabilizing	0.555	D	0.36	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.