TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30090	90493;90494;90495	chr2:178552632;178552631;178552630	chr2:179417359;179417358;179417357
N2AB	28449	85570;85571;85572	chr2:178552632;178552631;178552630	chr2:179417359;179417358;179417357
N2A	27522	82789;82790;82791	chr2:178552632;178552631;178552630	chr2:179417359;179417358;179417357
N2B	21025	63298;63299;63300	chr2:178552632;178552631;178552630	chr2:179417359;179417358;179417357
Novex-1	21150	63673;63674;63675	chr2:178552632;178552631;178552630	chr2:179417359;179417358;179417357
Novex-2	21217	63874;63875;63876	chr2:178552632;178552631;178552630	chr2:179417359;179417358;179417357
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-107
• Domain position: 61
• Structural Position: 93
• Q(SASA): 0.145
• 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
V/I	rs759865479	0.141	0.001	N	0.189	0.07	0.287603790349	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	1.11483E-04	None	0	None	0	0	0
V/I	rs759865479	0.141	0.001	N	0.189	0.07	0.287603790349	gnomAD-4.0.0	4.7892E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39655E-06	0	1.65645E-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
V/A	0.4759	ambiguous	0.3993	ambiguous	-1.803	Destabilizing	0.001	N	0.376	neutral	N	0.484417973	None	None	N
V/C	0.8447	likely_pathogenic	0.7977	pathogenic	-1.615	Destabilizing	0.909	D	0.713	prob.delet.	None	None	None	None	N
V/D	0.9193	likely_pathogenic	0.8709	pathogenic	-1.482	Destabilizing	0.667	D	0.823	deleterious	N	0.518651474	None	None	N
V/E	0.8662	likely_pathogenic	0.8132	pathogenic	-1.306	Destabilizing	0.567	D	0.795	deleterious	None	None	None	None	N
V/F	0.3425	ambiguous	0.2749	benign	-1.037	Destabilizing	0.497	N	0.737	prob.delet.	N	0.515609599	None	None	N
V/G	0.6807	likely_pathogenic	0.5964	pathogenic	-2.308	Highly Destabilizing	0.331	N	0.807	deleterious	D	0.537516197	None	None	N
V/H	0.9431	likely_pathogenic	0.9111	pathogenic	-1.808	Destabilizing	0.968	D	0.819	deleterious	None	None	None	None	N
V/I	0.0755	likely_benign	0.0686	benign	-0.433	Destabilizing	0.001	N	0.189	neutral	N	0.46743948	None	None	N
V/K	0.9165	likely_pathogenic	0.8848	pathogenic	-1.507	Destabilizing	0.567	D	0.794	deleterious	None	None	None	None	N
V/L	0.2598	likely_benign	0.2123	benign	-0.433	Destabilizing	0.02	N	0.613	neutral	N	0.519460237	None	None	N
V/M	0.2704	likely_benign	0.2174	benign	-0.596	Destabilizing	0.567	D	0.673	neutral	None	None	None	None	N
V/N	0.8393	likely_pathogenic	0.7514	pathogenic	-1.681	Destabilizing	0.726	D	0.821	deleterious	None	None	None	None	N
V/P	0.9425	likely_pathogenic	0.9214	pathogenic	-0.857	Destabilizing	0.726	D	0.787	deleterious	None	None	None	None	N
V/Q	0.8838	likely_pathogenic	0.8372	pathogenic	-1.547	Destabilizing	0.726	D	0.801	deleterious	None	None	None	None	N
V/R	0.9025	likely_pathogenic	0.8607	pathogenic	-1.32	Destabilizing	0.726	D	0.812	deleterious	None	None	None	None	N
V/S	0.7599	likely_pathogenic	0.6538	pathogenic	-2.425	Highly Destabilizing	0.396	N	0.796	deleterious	None	None	None	None	N
V/T	0.6092	likely_pathogenic	0.5153	ambiguous	-2.083	Highly Destabilizing	0.272	N	0.665	neutral	None	None	None	None	N
V/W	0.9468	likely_pathogenic	0.913	pathogenic	-1.333	Destabilizing	0.968	D	0.787	deleterious	None	None	None	None	N
V/Y	0.8032	likely_pathogenic	0.72	pathogenic	-0.988	Destabilizing	0.726	D	0.72	prob.delet.	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.