TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33054	99385;99386;99387	chr2:178538669;178538668;178538667	chr2:179403396;179403395;179403394
N2AB	31413	94462;94463;94464	chr2:178538669;178538668;178538667	chr2:179403396;179403395;179403394
N2A	30486	91681;91682;91683	chr2:178538669;178538668;178538667	chr2:179403396;179403395;179403394
N2B	23989	72190;72191;72192	chr2:178538669;178538668;178538667	chr2:179403396;179403395;179403394
Novex-1	24114	72565;72566;72567	chr2:178538669;178538668;178538667	chr2:179403396;179403395;179403394
Novex-2	24181	72766;72767;72768	chr2:178538669;178538668;178538667	chr2:179403396;179403395;179403394
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-129
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7199
• 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
K/Q	rs1553507202	None	0.957	N	0.281	0.171	0.315314060047	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs1553507202	None	0.957	N	0.281	0.171	0.315314060047	gnomAD-4.0.0	6.5722E-06	None	None	None	None	N	None	2.41359E-05	0	None	0	0	None	0	0	0	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
K/A	0.3567	ambiguous	0.402	ambiguous	-0.003	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	N
K/C	0.7531	likely_pathogenic	0.7951	pathogenic	-0.246	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/D	0.6226	likely_pathogenic	0.6644	pathogenic	0.074	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
K/E	0.2311	likely_benign	0.2426	benign	0.112	Stabilizing	0.992	D	0.539	neutral	N	0.479651055	None	None	N
K/F	0.8201	likely_pathogenic	0.8575	pathogenic	-0.04	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/G	0.4328	ambiguous	0.4872	ambiguous	-0.241	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
K/H	0.3584	ambiguous	0.4096	ambiguous	-0.416	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/I	0.4604	ambiguous	0.5071	ambiguous	0.559	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/L	0.3972	ambiguous	0.4491	ambiguous	0.559	Stabilizing	1.0	D	0.591	neutral	None	None	None	None	N
K/M	0.3254	likely_benign	0.3565	ambiguous	0.157	Stabilizing	1.0	D	0.705	prob.neutral	N	0.470839033	None	None	N
K/N	0.4669	ambiguous	0.5025	ambiguous	0.133	Stabilizing	0.999	D	0.69	prob.neutral	N	0.489217474	None	None	N
K/P	0.5251	ambiguous	0.5776	pathogenic	0.401	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/Q	0.1574	likely_benign	0.1715	benign	0.031	Stabilizing	0.957	D	0.281	neutral	N	0.495450013	None	None	N
K/R	0.0862	likely_benign	0.093	benign	-0.083	Destabilizing	0.996	D	0.561	neutral	N	0.47936584	None	None	N
K/S	0.4295	ambiguous	0.4645	ambiguous	-0.341	Destabilizing	0.997	D	0.606	neutral	None	None	None	None	N
K/T	0.1873	likely_benign	0.2007	benign	-0.143	Destabilizing	0.999	D	0.69	prob.neutral	N	0.461179937	None	None	N
K/V	0.4098	ambiguous	0.4586	ambiguous	0.401	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/W	0.7885	likely_pathogenic	0.8338	pathogenic	-0.064	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/Y	0.733	likely_pathogenic	0.7757	pathogenic	0.267	Stabilizing	1.0	D	0.671	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.