TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22615	68068;68069;68070	chr2:178579187;178579186;178579185	chr2:179443914;179443913;179443912
N2AB	20974	63145;63146;63147	chr2:178579187;178579186;178579185	chr2:179443914;179443913;179443912
N2A	20047	60364;60365;60366	chr2:178579187;178579186;178579185	chr2:179443914;179443913;179443912
N2B	13550	40873;40874;40875	chr2:178579187;178579186;178579185	chr2:179443914;179443913;179443912
Novex-1	13675	41248;41249;41250	chr2:178579187;178579186;178579185	chr2:179443914;179443913;179443912
Novex-2	13742	41449;41450;41451	chr2:178579187;178579186;178579185	chr2:179443914;179443913;179443912
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-127
• Domain position: 56
• Structural Position: 146
• Q(SASA): 0.706
• 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/I	rs372296363	0.715	0.998	N	0.601	0.478	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/I	rs372296363	0.715	0.998	N	0.601	0.478	None	gnomAD-4.0.0	9.55098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.42976E-05	0	3.0259E-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
K/A	0.7464	likely_pathogenic	0.701	pathogenic	-0.076	Destabilizing	0.97	D	0.435	neutral	None	None	None	None	N
K/C	0.9198	likely_pathogenic	0.8988	pathogenic	-0.224	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
K/D	0.9252	likely_pathogenic	0.9079	pathogenic	0.003	Stabilizing	0.996	D	0.409	neutral	None	None	None	None	N
K/E	0.6307	likely_pathogenic	0.5759	pathogenic	0.02	Stabilizing	0.961	D	0.421	neutral	N	0.473466083	None	None	N
K/F	0.9543	likely_pathogenic	0.9384	pathogenic	-0.178	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
K/G	0.8425	likely_pathogenic	0.8117	pathogenic	-0.311	Destabilizing	0.985	D	0.44	neutral	None	None	None	None	N
K/H	0.5744	likely_pathogenic	0.5405	ambiguous	-0.619	Destabilizing	0.999	D	0.458	neutral	None	None	None	None	N
K/I	0.696	likely_pathogenic	0.6389	pathogenic	0.471	Stabilizing	0.998	D	0.601	neutral	N	0.514120627	None	None	N
K/L	0.6591	likely_pathogenic	0.6128	pathogenic	0.471	Stabilizing	0.97	D	0.44	neutral	None	None	None	None	N
K/M	0.5956	likely_pathogenic	0.5534	ambiguous	0.296	Stabilizing	1.0	D	0.458	neutral	None	None	None	None	N
K/N	0.8293	likely_pathogenic	0.7976	pathogenic	0.125	Stabilizing	0.994	D	0.38	neutral	N	0.455376172	None	None	N
K/P	0.774	likely_pathogenic	0.7411	pathogenic	0.318	Stabilizing	0.999	D	0.447	neutral	None	None	None	None	N
K/Q	0.3501	ambiguous	0.3233	benign	-0.065	Destabilizing	0.989	D	0.397	neutral	N	0.48483787	None	None	N
K/R	0.0847	likely_benign	0.0835	benign	-0.16	Destabilizing	0.031	N	0.245	neutral	N	0.381017282	None	None	N
K/S	0.8526	likely_pathogenic	0.8227	pathogenic	-0.388	Destabilizing	0.985	D	0.405	neutral	None	None	None	None	N
K/T	0.6118	likely_pathogenic	0.5688	pathogenic	-0.215	Destabilizing	0.98	D	0.423	neutral	N	0.498228455	None	None	N
K/V	0.6786	likely_pathogenic	0.6303	pathogenic	0.318	Stabilizing	0.996	D	0.488	neutral	None	None	None	None	N
K/W	0.9337	likely_pathogenic	0.9204	pathogenic	-0.148	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
K/Y	0.8732	likely_pathogenic	0.8423	pathogenic	0.183	Stabilizing	0.999	D	0.551	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.