TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22837	68734;68735;68736	chr2:178578006;178578005;178578004	chr2:179442733;179442732;179442731
N2AB	21196	63811;63812;63813	chr2:178578006;178578005;178578004	chr2:179442733;179442732;179442731
N2A	20269	61030;61031;61032	chr2:178578006;178578005;178578004	chr2:179442733;179442732;179442731
N2B	13772	41539;41540;41541	chr2:178578006;178578005;178578004	chr2:179442733;179442732;179442731
Novex-1	13897	41914;41915;41916	chr2:178578006;178578005;178578004	chr2:179442733;179442732;179442731
Novex-2	13964	42115;42116;42117	chr2:178578006;178578005;178578004	chr2:179442733;179442732;179442731
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-53
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3932
• Predicted PPI site: I

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
V/L	None	None	0.944	N	0.459	0.115	0.380223377699	gnomAD-4.0.0	4.77934E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.58305E-06	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
V/A	0.2702	likely_benign	0.2474	benign	-0.903	Destabilizing	0.944	D	0.457	neutral	N	0.506221581	None	None	I
V/C	0.8018	likely_pathogenic	0.7769	pathogenic	-0.8	Destabilizing	1.0	D	0.72	deleterious	None	None	None	None	I
V/D	0.7577	likely_pathogenic	0.7282	pathogenic	-0.439	Destabilizing	0.997	D	0.799	deleterious	None	None	None	None	I
V/E	0.6034	likely_pathogenic	0.5853	pathogenic	-0.485	Destabilizing	0.997	D	0.717	prob.delet.	N	0.519132163	None	None	I
V/F	0.2123	likely_benign	0.1827	benign	-0.729	Destabilizing	0.999	D	0.673	prob.neutral	None	None	None	None	I
V/G	0.4679	ambiguous	0.4111	ambiguous	-1.143	Destabilizing	0.997	D	0.638	neutral	N	0.489798527	None	None	I
V/H	0.7645	likely_pathogenic	0.7292	pathogenic	-0.57	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
V/I	0.0804	likely_benign	0.0767	benign	-0.384	Destabilizing	0.957	D	0.521	neutral	None	None	None	None	I
V/K	0.5591	ambiguous	0.5347	ambiguous	-0.774	Destabilizing	0.997	D	0.727	deleterious	None	None	None	None	I
V/L	0.2092	likely_benign	0.1877	benign	-0.384	Destabilizing	0.944	D	0.459	neutral	N	0.470703498	None	None	I
V/M	0.1602	likely_benign	0.1388	benign	-0.413	Destabilizing	0.999	D	0.67	prob.neutral	N	0.511147398	None	None	I
V/N	0.5558	ambiguous	0.4933	ambiguous	-0.602	Destabilizing	0.997	D	0.789	deleterious	None	None	None	None	I
V/P	0.5958	likely_pathogenic	0.5598	ambiguous	-0.52	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
V/Q	0.5242	ambiguous	0.4943	ambiguous	-0.779	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
V/R	0.4741	ambiguous	0.4656	ambiguous	-0.254	Destabilizing	0.997	D	0.833	deleterious	None	None	None	None	I
V/S	0.4107	ambiguous	0.3617	ambiguous	-1.092	Destabilizing	0.99	D	0.526	neutral	None	None	None	None	I
V/T	0.2176	likely_benign	0.2004	benign	-1.027	Destabilizing	0.422	N	0.307	neutral	None	None	None	None	I
V/W	0.8631	likely_pathogenic	0.8418	pathogenic	-0.85	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
V/Y	0.6528	likely_pathogenic	0.6243	pathogenic	-0.555	Destabilizing	0.999	D	0.697	prob.delet.	None	None	None	None	I

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.