TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24033	72322;72323;72324	chr2:178574035;178574034;178574033	chr2:179438762;179438761;179438760
N2AB	22392	67399;67400;67401	chr2:178574035;178574034;178574033	chr2:179438762;179438761;179438760
N2A	21465	64618;64619;64620	chr2:178574035;178574034;178574033	chr2:179438762;179438761;179438760
N2B	14968	45127;45128;45129	chr2:178574035;178574034;178574033	chr2:179438762;179438761;179438760
Novex-1	15093	45502;45503;45504	chr2:178574035;178574034;178574033	chr2:179438762;179438761;179438760
Novex-2	15160	45703;45704;45705	chr2:178574035;178574034;178574033	chr2:179438762;179438761;179438760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-131
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.381
• 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
V/I	rs771227294	None	None	N	0.273	0.086	0.273503213844	gnomAD-4.0.0	1.59202E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-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
V/A	0.1017	likely_benign	0.1124	benign	-0.651	Destabilizing	None	N	0.17	neutral	N	0.426289078	None	None	N
V/C	0.6522	likely_pathogenic	0.6614	pathogenic	-0.577	Destabilizing	0.356	N	0.367	neutral	None	None	None	None	N
V/D	0.185	likely_benign	0.197	benign	-0.632	Destabilizing	0.055	N	0.391	neutral	N	0.457652135	None	None	N
V/E	0.1905	likely_benign	0.1955	benign	-0.729	Destabilizing	0.072	N	0.339	neutral	None	None	None	None	N
V/F	0.166	likely_benign	0.1854	benign	-0.806	Destabilizing	0.171	N	0.439	neutral	N	0.47995143	None	None	N
V/G	0.1299	likely_benign	0.1403	benign	-0.803	Destabilizing	0.012	N	0.349	neutral	N	0.489897839	None	None	N
V/H	0.4415	ambiguous	0.4597	ambiguous	-0.348	Destabilizing	0.628	D	0.41	neutral	None	None	None	None	N
V/I	0.0772	likely_benign	0.0825	benign	-0.387	Destabilizing	None	N	0.273	neutral	N	0.500152118	None	None	N
V/K	0.2576	likely_benign	0.2552	benign	-0.646	Destabilizing	0.072	N	0.354	neutral	None	None	None	None	N
V/L	0.1429	likely_benign	0.1558	benign	-0.387	Destabilizing	0.002	N	0.231	neutral	N	0.459921649	None	None	N
V/M	0.1215	likely_benign	0.1327	benign	-0.436	Destabilizing	0.214	N	0.359	neutral	None	None	None	None	N
V/N	0.1722	likely_benign	0.1845	benign	-0.372	Destabilizing	0.072	N	0.467	neutral	None	None	None	None	N
V/P	0.194	likely_benign	0.1985	benign	-0.441	Destabilizing	None	N	0.265	neutral	None	None	None	None	N
V/Q	0.2477	likely_benign	0.2565	benign	-0.611	Destabilizing	0.356	N	0.475	neutral	None	None	None	None	N
V/R	0.2477	likely_benign	0.2449	benign	-0.087	Destabilizing	0.214	N	0.498	neutral	None	None	None	None	N
V/S	0.1281	likely_benign	0.1338	benign	-0.685	Destabilizing	0.001	N	0.245	neutral	None	None	None	None	N
V/T	0.1394	likely_benign	0.1481	benign	-0.687	Destabilizing	0.031	N	0.301	neutral	None	None	None	None	N
V/W	0.6827	likely_pathogenic	0.6999	pathogenic	-0.913	Destabilizing	0.864	D	0.427	neutral	None	None	None	None	N
V/Y	0.4028	ambiguous	0.4276	ambiguous	-0.625	Destabilizing	0.356	N	0.411	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.