TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23449	70570;70571;70572	chr2:178575787;178575786;178575785	chr2:179440514;179440513;179440512
N2AB	21808	65647;65648;65649	chr2:178575787;178575786;178575785	chr2:179440514;179440513;179440512
N2A	20881	62866;62867;62868	chr2:178575787;178575786;178575785	chr2:179440514;179440513;179440512
N2B	14384	43375;43376;43377	chr2:178575787;178575786;178575785	chr2:179440514;179440513;179440512
Novex-1	14509	43750;43751;43752	chr2:178575787;178575786;178575785	chr2:179440514;179440513;179440512
Novex-2	14576	43951;43952;43953	chr2:178575787;178575786;178575785	chr2:179440514;179440513;179440512
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: Fn3-58
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.2379
• 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/N	rs957102264	None	0.919	N	0.318	0.15	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.4564	ambiguous	0.5089	ambiguous	-0.242	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
K/C	0.7639	likely_pathogenic	0.7872	pathogenic	-0.339	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/D	0.8638	likely_pathogenic	0.8916	pathogenic	-0.25	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/E	0.4226	ambiguous	0.4572	ambiguous	-0.248	Destabilizing	0.991	D	0.449	neutral	N	0.503066632	None	None	N
K/F	0.9412	likely_pathogenic	0.9461	pathogenic	-0.603	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/G	0.5686	likely_pathogenic	0.661	pathogenic	-0.457	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
K/H	0.5294	ambiguous	0.542	ambiguous	-0.961	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/I	0.688	likely_pathogenic	0.6707	pathogenic	0.251	Stabilizing	0.997	D	0.802	deleterious	None	None	None	None	N
K/L	0.6362	likely_pathogenic	0.6502	pathogenic	0.251	Stabilizing	0.99	D	0.654	neutral	None	None	None	None	N
K/M	0.4938	ambiguous	0.5045	ambiguous	0.421	Stabilizing	1.0	D	0.697	prob.neutral	N	0.497146042	None	None	N
K/N	0.7462	likely_pathogenic	0.7816	pathogenic	0.061	Stabilizing	0.919	D	0.318	neutral	N	0.468126327	None	None	N
K/P	0.7908	likely_pathogenic	0.8398	pathogenic	0.115	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/Q	0.2371	likely_benign	0.2568	benign	-0.283	Destabilizing	0.997	D	0.69	prob.neutral	N	0.474736146	None	None	N
K/R	0.0677	likely_benign	0.0735	benign	-0.061	Destabilizing	0.993	D	0.462	neutral	N	0.461684156	None	None	N
K/S	0.6057	likely_pathogenic	0.6612	pathogenic	-0.491	Destabilizing	0.998	D	0.475	neutral	None	None	None	None	N
K/T	0.4024	ambiguous	0.4529	ambiguous	-0.338	Destabilizing	0.997	D	0.633	neutral	N	0.476987417	None	None	N
K/V	0.5714	likely_pathogenic	0.5748	pathogenic	0.115	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
K/W	0.896	likely_pathogenic	0.9065	pathogenic	-0.517	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
K/Y	0.8607	likely_pathogenic	0.8675	pathogenic	-0.122	Destabilizing	0.998	D	0.779	deleterious	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.