TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15603	47032;47033;47034	chr2:178618743;178618742;178618741	chr2:179483470;179483469;179483468
N2AB	13962	42109;42110;42111	chr2:178618743;178618742;178618741	chr2:179483470;179483469;179483468
N2A	13035	39328;39329;39330	chr2:178618743;178618742;178618741	chr2:179483470;179483469;179483468
N2B	6538	19837;19838;19839	chr2:178618743;178618742;178618741	chr2:179483470;179483469;179483468
Novex-1	6663	20212;20213;20214	chr2:178618743;178618742;178618741	chr2:179483470;179483469;179483468
Novex-2	6730	20413;20414;20415	chr2:178618743;178618742;178618741	chr2:179483470;179483469;179483468
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-108
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2743
• 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/E	None	None	0.993	N	0.531	0.34	0.351830644314	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.6936	likely_pathogenic	0.8306	pathogenic	-0.98	Destabilizing	0.985	D	0.556	neutral	None	None	None	None	N
K/C	0.6888	likely_pathogenic	0.805	pathogenic	-0.951	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
K/D	0.9137	likely_pathogenic	0.9471	pathogenic	-0.209	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
K/E	0.4947	ambiguous	0.6411	pathogenic	-0.053	Destabilizing	0.993	D	0.531	neutral	N	0.471433552	None	None	N
K/F	0.7136	likely_pathogenic	0.8117	pathogenic	-0.633	Destabilizing	0.942	D	0.685	prob.neutral	None	None	None	None	N
K/G	0.781	likely_pathogenic	0.8808	pathogenic	-1.381	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	N
K/H	0.3658	ambiguous	0.4245	ambiguous	-1.695	Destabilizing	0.991	D	0.669	neutral	None	None	None	None	N
K/I	0.5056	ambiguous	0.6488	pathogenic	0.083	Stabilizing	0.994	D	0.731	prob.delet.	N	0.468645807	None	None	N
K/L	0.4044	ambiguous	0.5676	pathogenic	0.083	Stabilizing	0.97	D	0.619	neutral	None	None	None	None	N
K/M	0.334	likely_benign	0.4909	ambiguous	-0.001	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/N	0.7643	likely_pathogenic	0.839	pathogenic	-0.707	Destabilizing	0.998	D	0.517	neutral	N	0.470830125	None	None	N
K/P	0.9649	likely_pathogenic	0.9739	pathogenic	-0.243	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
K/Q	0.201	likely_benign	0.3069	benign	-0.719	Destabilizing	0.998	D	0.526	neutral	N	0.470001502	None	None	N
K/R	0.0692	likely_benign	0.0833	benign	-0.713	Destabilizing	0.98	D	0.531	neutral	N	0.459820515	None	None	N
K/S	0.7316	likely_pathogenic	0.8536	pathogenic	-1.487	Destabilizing	0.985	D	0.489	neutral	None	None	None	None	N
K/T	0.5175	ambiguous	0.6855	pathogenic	-1.097	Destabilizing	0.98	D	0.586	neutral	N	0.470228314	None	None	N
K/V	0.4999	ambiguous	0.66	pathogenic	-0.243	Destabilizing	0.97	D	0.639	neutral	None	None	None	None	N
K/W	0.6873	likely_pathogenic	0.7664	pathogenic	-0.455	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
K/Y	0.5788	likely_pathogenic	0.644	pathogenic	-0.157	Destabilizing	0.155	N	0.399	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.