TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23257	69994;69995;69996	chr2:178576363;178576362;178576361	chr2:179441090;179441089;179441088
N2AB	21616	65071;65072;65073	chr2:178576363;178576362;178576361	chr2:179441090;179441089;179441088
N2A	20689	62290;62291;62292	chr2:178576363;178576362;178576361	chr2:179441090;179441089;179441088
N2B	14192	42799;42800;42801	chr2:178576363;178576362;178576361	chr2:179441090;179441089;179441088
Novex-1	14317	43174;43175;43176	chr2:178576363;178576362;178576361	chr2:179441090;179441089;179441088
Novex-2	14384	43375;43376;43377	chr2:178576363;178576362;178576361	chr2:179441090;179441089;179441088
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-57
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0931
• 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
A/V	rs1710097395	None	0.142	N	0.371	0.3	0.218112801441	gnomAD-4.0.0	1.74597E-06	None	None	None	None	N	None	0	3.22373E-05	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
A/C	0.5738	likely_pathogenic	0.5975	pathogenic	-1.522	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/D	0.9946	likely_pathogenic	0.9956	pathogenic	-1.91	Destabilizing	0.998	D	0.863	deleterious	N	0.50361773	None	None	N
A/E	0.9854	likely_pathogenic	0.9871	pathogenic	-1.706	Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
A/F	0.8664	likely_pathogenic	0.8758	pathogenic	-0.731	Destabilizing	0.991	D	0.885	deleterious	None	None	None	None	N
A/G	0.5055	ambiguous	0.502	ambiguous	-1.441	Destabilizing	0.979	D	0.681	prob.neutral	N	0.502350282	None	None	N
A/H	0.9896	likely_pathogenic	0.9907	pathogenic	-1.924	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/I	0.2956	likely_benign	0.3325	benign	0.379	Stabilizing	0.938	D	0.77	deleterious	None	None	None	None	N
A/K	0.9937	likely_pathogenic	0.9936	pathogenic	-1.017	Destabilizing	0.995	D	0.837	deleterious	None	None	None	None	N
A/L	0.4243	ambiguous	0.4307	ambiguous	0.379	Stabilizing	0.938	D	0.709	prob.delet.	None	None	None	None	N
A/M	0.5905	likely_pathogenic	0.62	pathogenic	-0.154	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
A/N	0.9793	likely_pathogenic	0.9838	pathogenic	-1.358	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
A/P	0.9866	likely_pathogenic	0.9887	pathogenic	-0.017	Destabilizing	0.998	D	0.857	deleterious	N	0.50336424	None	None	N
A/Q	0.9755	likely_pathogenic	0.9765	pathogenic	-1.133	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
A/R	0.9819	likely_pathogenic	0.9817	pathogenic	-1.234	Destabilizing	0.995	D	0.851	deleterious	None	None	None	None	N
A/S	0.403	ambiguous	0.4303	ambiguous	-1.863	Destabilizing	0.979	D	0.673	neutral	N	0.503110751	None	None	N
A/T	0.277	likely_benign	0.3109	benign	-1.503	Destabilizing	0.958	D	0.711	prob.delet.	N	0.484499517	None	None	N
A/V	0.1179	likely_benign	0.1333	benign	-0.017	Destabilizing	0.142	N	0.371	neutral	N	0.387895687	None	None	N
A/W	0.9939	likely_pathogenic	0.9946	pathogenic	-1.415	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
A/Y	0.9673	likely_pathogenic	0.9696	pathogenic	-0.828	Destabilizing	0.995	D	0.893	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.