TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2218	6877;6878;6879	chr2:178775059;178775058;178775057	chr2:179639786;179639785;179639784
N2AB	2218	6877;6878;6879	chr2:178775059;178775058;178775057	chr2:179639786;179639785;179639784
N2A	2218	6877;6878;6879	chr2:178775059;178775058;178775057	chr2:179639786;179639785;179639784
N2B	2172	6739;6740;6741	chr2:178775059;178775058;178775057	chr2:179639786;179639785;179639784
Novex-1	2172	6739;6740;6741	chr2:178775059;178775058;178775057	chr2:179639786;179639785;179639784
Novex-2	2172	6739;6740;6741	chr2:178775059;178775058;178775057	chr2:179639786;179639785;179639784
Novex-3	2218	6877;6878;6879	chr2:178775059;178775058;178775057	chr2:179639786;179639785;179639784

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-11
• Domain position: 45
• Structural Position: 111
• Q(SASA): 0.8261
• 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
D/G	None	None	0.892	N	0.377	0.255	0.134241683229	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.1457	likely_benign	0.1464	benign	0.076	Stabilizing	0.805	D	0.356	neutral	N	0.341996669	None	None	N
D/C	0.5257	ambiguous	0.5342	ambiguous	-0.213	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
D/E	0.1203	likely_benign	0.1186	benign	-0.42	Destabilizing	0.025	N	0.254	neutral	N	0.351326325	None	None	N
D/F	0.3983	ambiguous	0.4083	ambiguous	-0.069	Destabilizing	0.999	D	0.476	neutral	None	None	None	None	N
D/G	0.1245	likely_benign	0.1254	benign	-0.004	Destabilizing	0.892	D	0.377	neutral	N	0.331192701	None	None	N
D/H	0.2032	likely_benign	0.2025	benign	0.599	Stabilizing	0.995	D	0.378	neutral	N	0.373923822	None	None	N
D/I	0.2227	likely_benign	0.2301	benign	0.217	Stabilizing	0.987	D	0.5	neutral	None	None	None	None	N
D/K	0.2104	likely_benign	0.2097	benign	0.386	Stabilizing	0.073	N	0.317	neutral	None	None	None	None	N
D/L	0.2442	likely_benign	0.2421	benign	0.217	Stabilizing	0.975	D	0.504	neutral	None	None	None	None	N
D/M	0.415	ambiguous	0.4199	ambiguous	-0.025	Destabilizing	0.999	D	0.507	neutral	None	None	None	None	N
D/N	0.0709	likely_benign	0.0705	benign	0.179	Stabilizing	0.967	D	0.379	neutral	N	0.352401363	None	None	N
D/P	0.3998	ambiguous	0.3977	ambiguous	0.187	Stabilizing	0.987	D	0.38	neutral	None	None	None	None	N
D/Q	0.2206	likely_benign	0.2185	benign	0.165	Stabilizing	0.95	D	0.414	neutral	None	None	None	None	N
D/R	0.2537	likely_benign	0.2535	benign	0.597	Stabilizing	0.95	D	0.399	neutral	None	None	None	None	N
D/S	0.0935	likely_benign	0.0924	benign	0.089	Stabilizing	0.916	D	0.365	neutral	None	None	None	None	N
D/T	0.1794	likely_benign	0.1811	benign	0.161	Stabilizing	0.975	D	0.37	neutral	None	None	None	None	N
D/V	0.1602	likely_benign	0.1622	benign	0.187	Stabilizing	0.967	D	0.504	neutral	N	0.374201043	None	None	N
D/W	0.745	likely_pathogenic	0.7542	pathogenic	-0.063	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
D/Y	0.1776	likely_benign	0.1818	benign	0.145	Stabilizing	0.999	D	0.479	neutral	N	0.440533599	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.