TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19161	57706;57707;57708	chr2:178597601;178597600;178597599	chr2:179462328;179462327;179462326
N2AB	17520	52783;52784;52785	chr2:178597601;178597600;178597599	chr2:179462328;179462327;179462326
N2A	16593	50002;50003;50004	chr2:178597601;178597600;178597599	chr2:179462328;179462327;179462326
N2B	10096	30511;30512;30513	chr2:178597601;178597600;178597599	chr2:179462328;179462327;179462326
Novex-1	10221	30886;30887;30888	chr2:178597601;178597600;178597599	chr2:179462328;179462327;179462326
Novex-2	10288	31087;31088;31089	chr2:178597601;178597600;178597599	chr2:179462328;179462327;179462326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-117
• Domain position: 67
• Structural Position: 154
• Q(SASA): 0.1546
• 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
Y/C	rs754992982	-1.697	1.0	D	0.854	0.868	0.845456798365	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.92E-06	0
Y/C	rs754992982	-1.697	1.0	D	0.854	0.868	0.845456798365	gnomAD-4.0.0	3.18544E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86599E-05	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
Y/A	0.997	likely_pathogenic	0.9984	pathogenic	-2.634	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/C	0.9349	likely_pathogenic	0.9716	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.854	deleterious	D	0.629278272	None	None	N
Y/D	0.999	likely_pathogenic	0.9994	pathogenic	-3.409	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.629278272	None	None	N
Y/E	0.9996	likely_pathogenic	0.9997	pathogenic	-3.173	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/F	0.1435	likely_benign	0.1776	benign	-0.947	Destabilizing	0.999	D	0.697	prob.neutral	D	0.575982202	None	None	N
Y/G	0.9953	likely_pathogenic	0.9972	pathogenic	-3.09	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/H	0.9795	likely_pathogenic	0.991	pathogenic	-2.22	Highly Destabilizing	1.0	D	0.787	deleterious	D	0.629076468	None	None	N
Y/I	0.9365	likely_pathogenic	0.9541	pathogenic	-1.119	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/K	0.9993	likely_pathogenic	0.9995	pathogenic	-2.205	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
Y/L	0.8885	likely_pathogenic	0.9095	pathogenic	-1.119	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
Y/M	0.9828	likely_pathogenic	0.9888	pathogenic	-1.17	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/N	0.9942	likely_pathogenic	0.997	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.629278272	None	None	N
Y/P	0.9985	likely_pathogenic	0.9992	pathogenic	-1.64	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/Q	0.9991	likely_pathogenic	0.9996	pathogenic	-2.759	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/R	0.9964	likely_pathogenic	0.9978	pathogenic	-2.282	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/S	0.9935	likely_pathogenic	0.9967	pathogenic	-3.468	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.629278272	None	None	N
Y/T	0.9972	likely_pathogenic	0.9986	pathogenic	-3.086	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/V	0.9287	likely_pathogenic	0.9485	pathogenic	-1.64	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/W	0.7554	likely_pathogenic	0.8312	pathogenic	-0.353	Destabilizing	1.0	D	0.783	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.