TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29619	89080;89081;89082	chr2:178554492;178554491;178554490	chr2:179419219;179419218;179419217
N2AB	27978	84157;84158;84159	chr2:178554492;178554491;178554490	chr2:179419219;179419218;179419217
N2A	27051	81376;81377;81378	chr2:178554492;178554491;178554490	chr2:179419219;179419218;179419217
N2B	20554	61885;61886;61887	chr2:178554492;178554491;178554490	chr2:179419219;179419218;179419217
Novex-1	20679	62260;62261;62262	chr2:178554492;178554491;178554490	chr2:179419219;179419218;179419217
Novex-2	20746	62461;62462;62463	chr2:178554492;178554491;178554490	chr2:179419219;179419218;179419217
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-103
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2984
• 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
P/L	rs1042897248	None	0.331	N	0.691	0.46	0.489589578638	gnomAD-4.0.0	6.84609E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16052E-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
P/A	0.0804	likely_benign	0.0726	benign	-1.744	Destabilizing	0.001	N	0.449	neutral	N	0.504914859	None	None	N
P/C	0.4706	ambiguous	0.4306	ambiguous	-1.015	Destabilizing	0.909	D	0.758	deleterious	None	None	None	None	N
P/D	0.7411	likely_pathogenic	0.6979	pathogenic	-1.854	Destabilizing	0.396	N	0.604	neutral	None	None	None	None	N
P/E	0.597	likely_pathogenic	0.5359	ambiguous	-1.855	Destabilizing	0.157	N	0.575	neutral	None	None	None	None	N
P/F	0.5413	ambiguous	0.5432	ambiguous	-1.326	Destabilizing	0.726	D	0.761	deleterious	None	None	None	None	N
P/G	0.3732	ambiguous	0.3256	benign	-2.055	Highly Destabilizing	0.157	N	0.595	neutral	None	None	None	None	N
P/H	0.394	ambiguous	0.3965	ambiguous	-1.587	Destabilizing	0.909	D	0.703	prob.neutral	None	None	None	None	N
P/I	0.4559	ambiguous	0.4028	ambiguous	-0.975	Destabilizing	0.567	D	0.729	prob.delet.	None	None	None	None	N
P/K	0.7233	likely_pathogenic	0.6729	pathogenic	-1.52	Destabilizing	0.157	N	0.579	neutral	None	None	None	None	N
P/L	0.3097	likely_benign	0.2894	benign	-0.975	Destabilizing	0.331	N	0.691	prob.neutral	N	0.497738245	None	None	N
P/M	0.4547	ambiguous	0.4204	ambiguous	-0.689	Destabilizing	0.909	D	0.705	prob.neutral	None	None	None	None	N
P/N	0.5875	likely_pathogenic	0.5411	ambiguous	-1.271	Destabilizing	0.396	N	0.668	neutral	None	None	None	None	N
P/Q	0.4284	ambiguous	0.4013	ambiguous	-1.478	Destabilizing	0.497	N	0.635	neutral	D	0.522225283	None	None	N
P/R	0.6123	likely_pathogenic	0.5788	pathogenic	-0.909	Destabilizing	0.497	N	0.683	prob.neutral	N	0.503614049	None	None	N
P/S	0.1629	likely_benign	0.1436	benign	-1.725	Destabilizing	0.001	N	0.364	neutral	N	0.486724335	None	None	N
P/T	0.2016	likely_benign	0.1757	benign	-1.636	Destabilizing	0.124	N	0.535	neutral	N	0.499259182	None	None	N
P/V	0.3023	likely_benign	0.263	benign	-1.199	Destabilizing	0.396	N	0.633	neutral	None	None	None	None	N
P/W	0.7088	likely_pathogenic	0.7162	pathogenic	-1.527	Destabilizing	0.968	D	0.719	prob.delet.	None	None	None	None	N
P/Y	0.534	ambiguous	0.5213	ambiguous	-1.284	Destabilizing	0.726	D	0.763	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.