TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32591	97996;97997;97998	chr2:178541306;178541305;178541304	chr2:179406033;179406032;179406031
N2AB	30950	93073;93074;93075	chr2:178541306;178541305;178541304	chr2:179406033;179406032;179406031
N2A	30023	90292;90293;90294	chr2:178541306;178541305;178541304	chr2:179406033;179406032;179406031
N2B	23526	70801;70802;70803	chr2:178541306;178541305;178541304	chr2:179406033;179406032;179406031
Novex-1	23651	71176;71177;71178	chr2:178541306;178541305;178541304	chr2:179406033;179406032;179406031
Novex-2	23718	71377;71378;71379	chr2:178541306;178541305;178541304	chr2:179406033;179406032;179406031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-125
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.492
• 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
P/H	None	None	0.993	N	0.717	0.413	0.563655836063	gnomAD-4.0.0	1.44754E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.87663E-06	0	0
P/R	None	None	0.868	N	0.731	0.283	0.494299846589	gnomAD-4.0.0	7.23772E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.74429E-05
P/T	None	None	0.483	N	0.485	0.151	0.337621943819	gnomAD-4.0.0	7.22291E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.74058E-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
P/A	0.0796	likely_benign	0.079	benign	-0.876	Destabilizing	0.278	N	0.499	neutral	N	0.517396658	None	None	N
P/C	0.4345	ambiguous	0.4694	ambiguous	-0.72	Destabilizing	0.995	D	0.781	deleterious	None	None	None	None	N
P/D	0.6599	likely_pathogenic	0.7285	pathogenic	-0.713	Destabilizing	0.712	D	0.551	neutral	None	None	None	None	N
P/E	0.4354	ambiguous	0.4941	ambiguous	-0.797	Destabilizing	0.712	D	0.545	neutral	None	None	None	None	N
P/F	0.5606	ambiguous	0.625	pathogenic	-0.848	Destabilizing	0.946	D	0.78	deleterious	None	None	None	None	N
P/G	0.2612	likely_benign	0.2975	benign	-1.072	Destabilizing	0.553	D	0.559	neutral	None	None	None	None	N
P/H	0.2986	likely_benign	0.3481	ambiguous	-0.501	Destabilizing	0.993	D	0.717	prob.delet.	N	0.512915299	None	None	N
P/I	0.3973	ambiguous	0.4438	ambiguous	-0.484	Destabilizing	0.032	N	0.547	neutral	None	None	None	None	N
P/K	0.3814	ambiguous	0.4442	ambiguous	-0.795	Destabilizing	0.712	D	0.553	neutral	None	None	None	None	N
P/L	0.2078	likely_benign	0.2487	benign	-0.484	Destabilizing	0.278	N	0.605	neutral	N	0.51126012	None	None	N
P/M	0.3594	ambiguous	0.4056	ambiguous	-0.436	Destabilizing	0.946	D	0.738	deleterious	None	None	None	None	N
P/N	0.393	ambiguous	0.4521	ambiguous	-0.535	Destabilizing	0.897	D	0.656	prob.neutral	None	None	None	None	N
P/Q	0.2334	likely_benign	0.2674	benign	-0.792	Destabilizing	0.946	D	0.617	neutral	None	None	None	None	N
P/R	0.2733	likely_benign	0.3209	benign	-0.17	Destabilizing	0.868	D	0.731	deleterious	N	0.488036641	None	None	N
P/S	0.1444	likely_benign	0.1616	benign	-0.935	Destabilizing	0.024	N	0.331	neutral	N	0.483250474	None	None	N
P/T	0.1243	likely_benign	0.1453	benign	-0.919	Destabilizing	0.483	N	0.485	neutral	N	0.494099801	None	None	N
P/V	0.2595	likely_benign	0.2833	benign	-0.579	Destabilizing	0.338	N	0.537	neutral	None	None	None	None	N
P/W	0.7002	likely_pathogenic	0.7669	pathogenic	-0.927	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
P/Y	0.501	ambiguous	0.5665	pathogenic	-0.659	Destabilizing	0.982	D	0.793	deleterious	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.