TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18946	57061;57062;57063	chr2:178598874;178598873;178598872	chr2:179463601;179463600;179463599
N2AB	17305	52138;52139;52140	chr2:178598874;178598873;178598872	chr2:179463601;179463600;179463599
N2A	16378	49357;49358;49359	chr2:178598874;178598873;178598872	chr2:179463601;179463600;179463599
N2B	9881	29866;29867;29868	chr2:178598874;178598873;178598872	chr2:179463601;179463600;179463599
Novex-1	10006	30241;30242;30243	chr2:178598874;178598873;178598872	chr2:179463601;179463600;179463599
Novex-2	10073	30442;30443;30444	chr2:178598874;178598873;178598872	chr2:179463601;179463600;179463599
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: Fn3-25
• Domain position: 63
• Structural Position: 89
• Q(SASA): 0.4085
• 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/A	None	None	0.994	N	0.397	0.243	0.480574121323	gnomAD-4.0.0	1.59226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85994E-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	0.4125	ambiguous	0.3686	ambiguous	-1.608	Destabilizing	0.994	D	0.397	neutral	N	0.485960952	None	None	N
V/C	0.7916	likely_pathogenic	0.7365	pathogenic	-1.175	Destabilizing	1.0	D	0.533	neutral	None	None	None	None	N
V/D	0.6587	likely_pathogenic	0.6144	pathogenic	-1.847	Destabilizing	0.994	D	0.527	neutral	N	0.464836318	None	None	N
V/E	0.545	ambiguous	0.5047	ambiguous	-1.634	Destabilizing	0.998	D	0.441	neutral	None	None	None	None	N
V/F	0.3044	likely_benign	0.2902	benign	-0.936	Destabilizing	0.999	D	0.497	neutral	N	0.461622654	None	None	N
V/G	0.4676	ambiguous	0.3933	ambiguous	-2.14	Highly Destabilizing	0.989	D	0.507	neutral	N	0.505162788	None	None	N
V/H	0.8078	likely_pathogenic	0.757	pathogenic	-1.932	Destabilizing	1.0	D	0.618	neutral	None	None	None	None	N
V/I	0.0851	likely_benign	0.0881	benign	-0.141	Destabilizing	0.998	D	0.415	neutral	N	0.475186598	None	None	N
V/K	0.6192	likely_pathogenic	0.5708	pathogenic	-1.18	Destabilizing	0.998	D	0.453	neutral	None	None	None	None	N
V/L	0.3681	ambiguous	0.3645	ambiguous	-0.141	Destabilizing	0.987	D	0.421	neutral	N	0.377041188	None	None	N
V/M	0.2528	likely_benign	0.2451	benign	-0.259	Destabilizing	1.0	D	0.486	neutral	None	None	None	None	N
V/N	0.4319	ambiguous	0.3397	benign	-1.438	Destabilizing	0.611	D	0.375	neutral	None	None	None	None	N
V/P	0.8334	likely_pathogenic	0.7294	pathogenic	-0.6	Destabilizing	1.0	D	0.529	neutral	None	None	None	None	N
V/Q	0.5674	likely_pathogenic	0.5048	ambiguous	-1.265	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
V/R	0.5957	likely_pathogenic	0.5501	ambiguous	-1.173	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
V/S	0.4737	ambiguous	0.3915	ambiguous	-2.087	Highly Destabilizing	0.992	D	0.437	neutral	None	None	None	None	N
V/T	0.3404	ambiguous	0.2975	benign	-1.714	Destabilizing	0.992	D	0.389	neutral	None	None	None	None	N
V/W	0.9184	likely_pathogenic	0.9146	pathogenic	-1.396	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
V/Y	0.7297	likely_pathogenic	0.6884	pathogenic	-0.947	Destabilizing	1.0	D	0.503	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.