TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14162	42709;42710;42711	chr2:178634015;178634014;178634013	chr2:179498742;179498741;179498740
N2AB	12521	37786;37787;37788	chr2:178634015;178634014;178634013	chr2:179498742;179498741;179498740
N2A	11594	35005;35006;35007	chr2:178634015;178634014;178634013	chr2:179498742;179498741;179498740
N2B	5097	15514;15515;15516	chr2:178634015;178634014;178634013	chr2:179498742;179498741;179498740
Novex-1	5222	15889;15890;15891	chr2:178634015;178634014;178634013	chr2:179498742;179498741;179498740
Novex-2	5289	16090;16091;16092	chr2:178634015;178634014;178634013	chr2:179498742;179498741;179498740
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-92
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5428
• 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/A	None	None	0.047	N	0.289	0.121	0.454893017966	gnomAD-4.0.0	3.18434E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88296E-05	0	2.86012E-06	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
V/A	0.1131	likely_benign	0.1247	benign	-1.494	Destabilizing	0.047	N	0.289	neutral	N	0.478848581	None	None	N
V/C	0.5029	ambiguous	0.5811	pathogenic	-0.952	Destabilizing	0.983	D	0.487	neutral	None	None	None	None	N
V/D	0.2031	likely_benign	0.2357	benign	-1.26	Destabilizing	0.101	N	0.469	neutral	N	0.441423793	None	None	N
V/E	0.1284	likely_benign	0.1611	benign	-1.243	Destabilizing	None	N	0.386	neutral	None	None	None	None	N
V/F	0.1289	likely_benign	0.127	benign	-1.126	Destabilizing	0.794	D	0.523	neutral	N	0.473552143	None	None	N
V/G	0.1871	likely_benign	0.193	benign	-1.838	Destabilizing	0.351	N	0.513	neutral	N	0.490136297	None	None	N
V/H	0.2439	likely_benign	0.3133	benign	-1.411	Destabilizing	0.836	D	0.51	neutral	None	None	None	None	N
V/I	0.0697	likely_benign	0.0724	benign	-0.644	Destabilizing	0.101	N	0.443	neutral	N	0.481512423	None	None	N
V/K	0.1388	likely_benign	0.1761	benign	-1.205	Destabilizing	0.129	N	0.476	neutral	None	None	None	None	N
V/L	0.1298	likely_benign	0.1365	benign	-0.644	Destabilizing	0.101	N	0.381	neutral	N	0.472667222	None	None	N
V/M	0.1147	likely_benign	0.1292	benign	-0.486	Destabilizing	0.836	D	0.482	neutral	None	None	None	None	N
V/N	0.153	likely_benign	0.1719	benign	-0.994	Destabilizing	0.418	N	0.523	neutral	None	None	None	None	N
V/P	0.764	likely_pathogenic	0.7887	pathogenic	-0.893	Destabilizing	0.593	D	0.533	neutral	None	None	None	None	N
V/Q	0.1319	likely_benign	0.1705	benign	-1.135	Destabilizing	0.01	N	0.388	neutral	None	None	None	None	N
V/R	0.1325	likely_benign	0.1537	benign	-0.731	Destabilizing	0.264	N	0.519	neutral	None	None	None	None	N
V/S	0.1038	likely_benign	0.113	benign	-1.541	Destabilizing	0.129	N	0.463	neutral	None	None	None	None	N
V/T	0.0845	likely_benign	0.1057	benign	-1.41	Destabilizing	0.001	N	0.195	neutral	None	None	None	None	N
V/W	0.6177	likely_pathogenic	0.6932	pathogenic	-1.347	Destabilizing	0.983	D	0.517	neutral	None	None	None	None	N
V/Y	0.3383	likely_benign	0.3849	ambiguous	-1.04	Destabilizing	0.836	D	0.545	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.