TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16223	48892;48893;48894	chr2:178614940;178614939;178614938	chr2:179479667;179479666;179479665
N2AB	14582	43969;43970;43971	chr2:178614940;178614939;178614938	chr2:179479667;179479666;179479665
N2A	13655	41188;41189;41190	chr2:178614940;178614939;178614938	chr2:179479667;179479666;179479665
N2B	7158	21697;21698;21699	chr2:178614940;178614939;178614938	chr2:179479667;179479666;179479665
Novex-1	7283	22072;22073;22074	chr2:178614940;178614939;178614938	chr2:179479667;179479666;179479665
Novex-2	7350	22273;22274;22275	chr2:178614940;178614939;178614938	chr2:179479667;179479666;179479665
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: Fn3-5
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.4141
• 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/T	rs1553704101	None	0.055	N	0.305	0.172	0.186928172975	gnomAD-4.0.0	6.92033E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.19795E-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
K/A	0.215	likely_benign	0.2675	benign	-0.803	Destabilizing	0.016	N	0.303	neutral	None	None	None	None	N
K/C	0.4407	ambiguous	0.5066	ambiguous	-0.518	Destabilizing	0.864	D	0.327	neutral	None	None	None	None	N
K/D	0.4705	ambiguous	0.537	ambiguous	-0.473	Destabilizing	None	N	0.124	neutral	None	None	None	None	N
K/E	0.1267	likely_benign	0.1447	benign	-0.318	Destabilizing	None	N	0.074	neutral	N	0.463313963	None	None	N
K/F	0.6452	likely_pathogenic	0.7043	pathogenic	-0.233	Destabilizing	0.628	D	0.381	neutral	None	None	None	None	N
K/G	0.3128	likely_benign	0.3676	ambiguous	-1.212	Destabilizing	0.031	N	0.253	neutral	None	None	None	None	N
K/H	0.2001	likely_benign	0.2326	benign	-1.471	Destabilizing	0.214	N	0.375	neutral	None	None	None	None	N
K/I	0.2744	likely_benign	0.3324	benign	0.29	Stabilizing	0.295	N	0.419	neutral	N	0.480775871	None	None	N
K/L	0.2307	likely_benign	0.2993	benign	0.29	Stabilizing	0.072	N	0.301	neutral	None	None	None	None	N
K/M	0.1529	likely_benign	0.1791	benign	0.127	Stabilizing	0.356	N	0.37	neutral	None	None	None	None	N
K/N	0.2539	likely_benign	0.3108	benign	-0.729	Destabilizing	0.055	N	0.225	neutral	N	0.474279092	None	None	N
K/P	0.9443	likely_pathogenic	0.9595	pathogenic	-0.046	Destabilizing	0.136	N	0.425	neutral	None	None	None	None	N
K/Q	0.0709	likely_benign	0.083	benign	-0.659	Destabilizing	None	N	0.049	neutral	N	0.418736457	None	None	N
K/R	0.0871	likely_benign	0.0836	benign	-0.825	Destabilizing	0.012	N	0.258	neutral	N	0.460828366	None	None	N
K/S	0.2301	likely_benign	0.286	benign	-1.291	Destabilizing	0.016	N	0.285	neutral	None	None	None	None	N
K/T	0.1129	likely_benign	0.1454	benign	-0.919	Destabilizing	0.055	N	0.305	neutral	N	0.439358583	None	None	N
K/V	0.2113	likely_benign	0.2632	benign	-0.046	Destabilizing	0.072	N	0.367	neutral	None	None	None	None	N
K/W	0.7606	likely_pathogenic	0.7843	pathogenic	-0.167	Destabilizing	0.864	D	0.361	neutral	None	None	None	None	N
K/Y	0.5385	ambiguous	0.5822	pathogenic	0.067	Stabilizing	0.356	N	0.375	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.