TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23193	69802;69803;69804	chr2:178576667;178576666;178576665	chr2:179441394;179441393;179441392
N2AB	21552	64879;64880;64881	chr2:178576667;178576666;178576665	chr2:179441394;179441393;179441392
N2A	20625	62098;62099;62100	chr2:178576667;178576666;178576665	chr2:179441394;179441393;179441392
N2B	14128	42607;42608;42609	chr2:178576667;178576666;178576665	chr2:179441394;179441393;179441392
Novex-1	14253	42982;42983;42984	chr2:178576667;178576666;178576665	chr2:179441394;179441393;179441392
Novex-2	14320	43183;43184;43185	chr2:178576667;178576666;178576665	chr2:179441394;179441393;179441392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-56
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3517
• 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/L	None	None	0.92	N	0.491	0.324	0.589282225109	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02499E-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	0.063	likely_benign	0.069	benign	-0.921	Destabilizing	0.704	D	0.403	neutral	N	0.481461996	None	None	N
P/C	0.48	ambiguous	0.5368	ambiguous	-0.651	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
P/D	0.751	likely_pathogenic	0.7629	pathogenic	-0.654	Destabilizing	0.939	D	0.401	neutral	None	None	None	None	N
P/E	0.5003	ambiguous	0.5292	ambiguous	-0.751	Destabilizing	0.939	D	0.378	neutral	None	None	None	None	N
P/F	0.6065	likely_pathogenic	0.6439	pathogenic	-0.993	Destabilizing	0.997	D	0.513	neutral	None	None	None	None	N
P/G	0.3624	ambiguous	0.391	ambiguous	-1.11	Destabilizing	0.939	D	0.456	neutral	None	None	None	None	N
P/H	0.3099	likely_benign	0.3432	ambiguous	-0.701	Destabilizing	0.999	D	0.449	neutral	None	None	None	None	N
P/I	0.2674	likely_benign	0.3005	benign	-0.553	Destabilizing	0.982	D	0.506	neutral	None	None	None	None	N
P/K	0.388	ambiguous	0.4332	ambiguous	-0.745	Destabilizing	0.939	D	0.388	neutral	None	None	None	None	N
P/L	0.1203	likely_benign	0.1352	benign	-0.553	Destabilizing	0.92	D	0.491	neutral	N	0.500375831	None	None	N
P/M	0.2796	likely_benign	0.3105	benign	-0.406	Destabilizing	0.999	D	0.452	neutral	None	None	None	None	N
P/N	0.4655	ambiguous	0.4874	ambiguous	-0.398	Destabilizing	0.939	D	0.433	neutral	None	None	None	None	N
P/Q	0.2181	likely_benign	0.2548	benign	-0.676	Destabilizing	0.988	D	0.413	neutral	D	0.52325269	None	None	N
P/R	0.2494	likely_benign	0.2895	benign	-0.183	Destabilizing	0.988	D	0.463	neutral	N	0.490137407	None	None	N
P/S	0.152	likely_benign	0.1665	benign	-0.8	Destabilizing	0.159	N	0.199	neutral	N	0.487022531	None	None	N
P/T	0.1011	likely_benign	0.1071	benign	-0.8	Destabilizing	0.061	N	0.195	neutral	N	0.463801742	None	None	N
P/V	0.1639	likely_benign	0.1818	benign	-0.64	Destabilizing	0.939	D	0.453	neutral	None	None	None	None	N
P/W	0.7642	likely_pathogenic	0.7983	pathogenic	-1.067	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
P/Y	0.5898	likely_pathogenic	0.6294	pathogenic	-0.79	Destabilizing	0.997	D	0.513	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.