TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20708	62347;62348;62349	chr2:178589603;178589602;178589601	chr2:179454330;179454329;179454328
N2AB	19067	57424;57425;57426	chr2:178589603;178589602;178589601	chr2:179454330;179454329;179454328
N2A	18140	54643;54644;54645	chr2:178589603;178589602;178589601	chr2:179454330;179454329;179454328
N2B	11643	35152;35153;35154	chr2:178589603;178589602;178589601	chr2:179454330;179454329;179454328
Novex-1	11768	35527;35528;35529	chr2:178589603;178589602;178589601	chr2:179454330;179454329;179454328
Novex-2	11835	35728;35729;35730	chr2:178589603;178589602;178589601	chr2:179454330;179454329;179454328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-38
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.3751
• 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
R/S	rs377175428	-2.108	0.201	N	0.446	0.192	0.200317383148	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.95E-06	0
R/S	rs377175428	-2.108	0.201	N	0.446	0.192	0.200317383148	gnomAD-4.0.0	4.10639E-06	None	None	None	None	N	None	0	2.23714E-05	None	0	0	None	0	0	3.59857E-06	0	1.65684E-05

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
R/A	0.8807	likely_pathogenic	0.9265	pathogenic	-2.033	Highly Destabilizing	0.25	N	0.427	neutral	None	None	None	None	N
R/C	0.3003	likely_benign	0.4406	ambiguous	-1.952	Destabilizing	0.992	D	0.547	neutral	None	None	None	None	N
R/D	0.9857	likely_pathogenic	0.9917	pathogenic	-0.737	Destabilizing	0.617	D	0.509	neutral	None	None	None	None	N
R/E	0.8776	likely_pathogenic	0.918	pathogenic	-0.538	Destabilizing	0.25	N	0.391	neutral	None	None	None	None	N
R/F	0.8818	likely_pathogenic	0.9175	pathogenic	-1.422	Destabilizing	0.972	D	0.565	neutral	None	None	None	None	N
R/G	0.8028	likely_pathogenic	0.8746	pathogenic	-2.382	Highly Destabilizing	0.549	D	0.506	neutral	N	0.482475282	None	None	N
R/H	0.2507	likely_benign	0.3174	benign	-2.203	Highly Destabilizing	0.92	D	0.518	neutral	None	None	None	None	N
R/I	0.8202	likely_pathogenic	0.8541	pathogenic	-1.032	Destabilizing	0.92	D	0.576	neutral	None	None	None	None	N
R/K	0.122	likely_benign	0.1679	benign	-1.454	Destabilizing	0.001	N	0.118	neutral	N	0.384204808	None	None	N
R/L	0.6679	likely_pathogenic	0.7279	pathogenic	-1.032	Destabilizing	0.617	D	0.506	neutral	None	None	None	None	N
R/M	0.6885	likely_pathogenic	0.7596	pathogenic	-1.42	Destabilizing	0.963	D	0.551	neutral	N	0.520215172	None	None	N
R/N	0.9421	likely_pathogenic	0.9638	pathogenic	-1.221	Destabilizing	0.617	D	0.427	neutral	None	None	None	None	N
R/P	0.9946	likely_pathogenic	0.9971	pathogenic	-1.353	Destabilizing	0.766	D	0.57	neutral	None	None	None	None	N
R/Q	0.2442	likely_benign	0.3043	benign	-1.245	Destabilizing	0.447	N	0.429	neutral	None	None	None	None	N
R/S	0.9291	likely_pathogenic	0.9623	pathogenic	-2.258	Highly Destabilizing	0.201	N	0.446	neutral	N	0.494719295	None	None	N
R/T	0.9024	likely_pathogenic	0.9341	pathogenic	-1.843	Destabilizing	0.549	D	0.487	neutral	N	0.505611079	None	None	N
R/V	0.8485	likely_pathogenic	0.8884	pathogenic	-1.353	Destabilizing	0.617	D	0.545	neutral	None	None	None	None	N
R/W	0.6637	likely_pathogenic	0.7417	pathogenic	-0.841	Destabilizing	0.99	D	0.582	neutral	N	0.519001664	None	None	N
R/Y	0.7827	likely_pathogenic	0.8432	pathogenic	-0.697	Destabilizing	0.972	D	0.57	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.