TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25749	77470;77471;77472	chr2:178568887;178568886;178568885	chr2:179433614;179433613;179433612
N2AB	24108	72547;72548;72549	chr2:178568887;178568886;178568885	chr2:179433614;179433613;179433612
N2A	23181	69766;69767;69768	chr2:178568887;178568886;178568885	chr2:179433614;179433613;179433612
N2B	16684	50275;50276;50277	chr2:178568887;178568886;178568885	chr2:179433614;179433613;179433612
Novex-1	16809	50650;50651;50652	chr2:178568887;178568886;178568885	chr2:179433614;179433613;179433612
Novex-2	16876	50851;50852;50853	chr2:178568887;178568886;178568885	chr2:179433614;179433613;179433612
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: Fn3-75
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.2218
• 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
A/V	None	None	0.524	N	0.419	0.18	0.26169431596	gnomAD-4.0.0	1.59288E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89408E-05	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	0.4128	ambiguous	0.4046	ambiguous	-0.836	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
A/D	0.6027	likely_pathogenic	0.5663	pathogenic	-1.423	Destabilizing	0.989	D	0.679	prob.neutral	N	0.504106782	None	None	N
A/E	0.4755	ambiguous	0.4457	ambiguous	-1.427	Destabilizing	0.994	D	0.664	neutral	None	None	None	None	N
A/F	0.484	ambiguous	0.453	ambiguous	-0.966	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
A/G	0.2126	likely_benign	0.1975	benign	-1.229	Destabilizing	0.008	N	0.474	neutral	N	0.46087608	None	None	N
A/H	0.6333	likely_pathogenic	0.6116	pathogenic	-1.488	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
A/I	0.3047	likely_benign	0.2767	benign	-0.305	Destabilizing	0.995	D	0.652	neutral	None	None	None	None	N
A/K	0.6711	likely_pathogenic	0.6428	pathogenic	-1.384	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
A/L	0.2261	likely_benign	0.2106	benign	-0.305	Destabilizing	0.984	D	0.522	neutral	None	None	None	None	N
A/M	0.2629	likely_benign	0.2465	benign	-0.216	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
A/N	0.4256	ambiguous	0.4015	ambiguous	-1.129	Destabilizing	0.933	D	0.696	prob.neutral	None	None	None	None	N
A/P	0.9422	likely_pathogenic	0.9272	pathogenic	-0.476	Destabilizing	0.994	D	0.702	prob.neutral	N	0.471266653	None	None	N
A/Q	0.4412	ambiguous	0.4215	ambiguous	-1.244	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
A/R	0.6046	likely_pathogenic	0.587	pathogenic	-1.05	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
A/S	0.1096	likely_benign	0.1035	benign	-1.447	Destabilizing	0.484	N	0.523	neutral	N	0.471127572	None	None	N
A/T	0.0821	likely_benign	0.08	benign	-1.358	Destabilizing	0.34	N	0.415	neutral	N	0.453907248	None	None	N
A/V	0.1506	likely_benign	0.1404	benign	-0.476	Destabilizing	0.524	D	0.419	neutral	N	0.487657249	None	None	N
A/W	0.8997	likely_pathogenic	0.8893	pathogenic	-1.4	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
A/Y	0.6692	likely_pathogenic	0.6375	pathogenic	-0.973	Destabilizing	1.0	D	0.707	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.