TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1380	4363;4364;4365	chr2:178778944;178778943;178778942	chr2:179643671;179643670;179643669
N2AB	1380	4363;4364;4365	chr2:178778944;178778943;178778942	chr2:179643671;179643670;179643669
N2A	1380	4363;4364;4365	chr2:178778944;178778943;178778942	chr2:179643671;179643670;179643669
N2B	1334	4225;4226;4227	chr2:178778944;178778943;178778942	chr2:179643671;179643670;179643669
Novex-1	1334	4225;4226;4227	chr2:178778944;178778943;178778942	chr2:179643671;179643670;179643669
Novex-2	1334	4225;4226;4227	chr2:178778944;178778943;178778942	chr2:179643671;179643670;179643669
Novex-3	1380	4363;4364;4365	chr2:178778944;178778943;178778942	chr2:179643671;179643670;179643669

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-5
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.3937
• 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	None	None	1.0	D	0.757	0.459	0.730598733731	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
Y/A	0.8679	likely_pathogenic	0.903	pathogenic	-2.122	Highly Destabilizing	0.998	D	0.663	neutral	None	None	None	None	N
Y/C	0.6089	likely_pathogenic	0.6467	pathogenic	-0.495	Destabilizing	1.0	D	0.757	deleterious	D	0.556594979	None	None	N
Y/D	0.8916	likely_pathogenic	0.9035	pathogenic	-0.809	Destabilizing	1.0	D	0.792	deleterious	N	0.480117014	None	None	N
Y/E	0.9388	likely_pathogenic	0.9499	pathogenic	-0.763	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
Y/F	0.1317	likely_benign	0.1345	benign	-1.041	Destabilizing	0.434	N	0.315	neutral	N	0.501326296	None	None	N
Y/G	0.9075	likely_pathogenic	0.9304	pathogenic	-2.408	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
Y/H	0.5353	ambiguous	0.5758	pathogenic	-0.961	Destabilizing	1.0	D	0.681	prob.neutral	N	0.484760861	None	None	N
Y/I	0.7109	likely_pathogenic	0.7341	pathogenic	-1.271	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
Y/K	0.9399	likely_pathogenic	0.9527	pathogenic	-0.946	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
Y/L	0.6181	likely_pathogenic	0.6736	pathogenic	-1.271	Destabilizing	0.994	D	0.59	neutral	None	None	None	None	N
Y/M	0.8127	likely_pathogenic	0.8366	pathogenic	-0.78	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
Y/N	0.6939	likely_pathogenic	0.7179	pathogenic	-1.13	Destabilizing	1.0	D	0.775	deleterious	N	0.464699722	None	None	N
Y/P	0.9913	likely_pathogenic	0.9944	pathogenic	-1.548	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
Y/Q	0.8815	likely_pathogenic	0.9105	pathogenic	-1.128	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
Y/R	0.8419	likely_pathogenic	0.8804	pathogenic	-0.458	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
Y/S	0.6467	likely_pathogenic	0.693	pathogenic	-1.564	Destabilizing	1.0	D	0.755	deleterious	N	0.472719022	None	None	N
Y/T	0.8014	likely_pathogenic	0.8177	pathogenic	-1.432	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
Y/V	0.6379	likely_pathogenic	0.6766	pathogenic	-1.548	Destabilizing	0.997	D	0.67	neutral	None	None	None	None	N
Y/W	0.6956	likely_pathogenic	0.7114	pathogenic	-0.769	Destabilizing	1.0	D	0.657	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.