TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24242	72949;72950;72951	chr2:178573408;178573407;178573406	chr2:179438135;179438134;179438133
N2AB	22601	68026;68027;68028	chr2:178573408;178573407;178573406	chr2:179438135;179438134;179438133
N2A	21674	65245;65246;65247	chr2:178573408;178573407;178573406	chr2:179438135;179438134;179438133
N2B	15177	45754;45755;45756	chr2:178573408;178573407;178573406	chr2:179438135;179438134;179438133
Novex-1	15302	46129;46130;46131	chr2:178573408;178573407;178573406	chr2:179438135;179438134;179438133
Novex-2	15369	46330;46331;46332	chr2:178573408;178573407;178573406	chr2:179438135;179438134;179438133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-64
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1912
• 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
C/S	None	None	0.058	N	0.399	0.249	0.424430313326	gnomAD-4.0.0	1.86391E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.25203E-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
C/A	0.34	ambiguous	0.3733	ambiguous	-1.56	Destabilizing	0.559	D	0.395	neutral	None	None	None	None	N
C/D	0.7897	likely_pathogenic	0.8171	pathogenic	-1.042	Destabilizing	0.956	D	0.717	prob.delet.	None	None	None	None	N
C/E	0.8069	likely_pathogenic	0.8323	pathogenic	-0.86	Destabilizing	0.956	D	0.748	deleterious	None	None	None	None	N
C/F	0.2484	likely_benign	0.2492	benign	-0.908	Destabilizing	0.97	D	0.749	deleterious	N	0.47446943	None	None	N
C/G	0.2172	likely_benign	0.2161	benign	-1.9	Destabilizing	0.698	D	0.625	neutral	N	0.471341003	None	None	N
C/H	0.5198	ambiguous	0.5425	ambiguous	-2.112	Highly Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
C/I	0.4397	ambiguous	0.4417	ambiguous	-0.658	Destabilizing	0.978	D	0.548	neutral	None	None	None	None	N
C/K	0.8204	likely_pathogenic	0.8319	pathogenic	-1.18	Destabilizing	0.956	D	0.7	prob.neutral	None	None	None	None	N
C/L	0.4073	ambiguous	0.437	ambiguous	-0.658	Destabilizing	0.86	D	0.473	neutral	None	None	None	None	N
C/M	0.4879	ambiguous	0.5278	ambiguous	0.297	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	N
C/N	0.4259	ambiguous	0.4564	ambiguous	-1.528	Destabilizing	0.956	D	0.748	deleterious	None	None	None	None	N
C/P	0.987	likely_pathogenic	0.9883	pathogenic	-0.934	Destabilizing	0.978	D	0.794	deleterious	None	None	None	None	N
C/Q	0.5877	likely_pathogenic	0.6151	pathogenic	-1.192	Destabilizing	0.956	D	0.811	deleterious	None	None	None	None	N
C/R	0.528	ambiguous	0.5346	ambiguous	-1.351	Destabilizing	0.942	D	0.803	deleterious	N	0.465913753	None	None	N
C/S	0.1821	likely_benign	0.196	benign	-1.9	Destabilizing	0.058	N	0.399	neutral	N	0.381214857	None	None	N
C/T	0.2638	likely_benign	0.2855	benign	-1.539	Destabilizing	0.754	D	0.485	neutral	None	None	None	None	N
C/V	0.3497	ambiguous	0.3627	ambiguous	-0.934	Destabilizing	0.86	D	0.511	neutral	None	None	None	None	N
C/W	0.624	likely_pathogenic	0.6442	pathogenic	-1.202	Destabilizing	0.997	D	0.745	deleterious	N	0.467632575	None	None	N
C/Y	0.3801	ambiguous	0.382	ambiguous	-1.055	Destabilizing	0.99	D	0.758	deleterious	N	0.47421594	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.