TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33257	99994;99995;99996	chr2:178537438;178537437;178537436	chr2:179402165;179402164;179402163
N2AB	31616	95071;95072;95073	chr2:178537438;178537437;178537436	chr2:179402165;179402164;179402163
N2A	30689	92290;92291;92292	chr2:178537438;178537437;178537436	chr2:179402165;179402164;179402163
N2B	24192	72799;72800;72801	chr2:178537438;178537437;178537436	chr2:179402165;179402164;179402163
Novex-1	24317	73174;73175;73176	chr2:178537438;178537437;178537436	chr2:179402165;179402164;179402163
Novex-2	24384	73375;73376;73377	chr2:178537438;178537437;178537436	chr2:179402165;179402164;179402163
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-157
• Domain position: 55
• Structural Position: 141
• Q(SASA): 0.3979
• 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	rs766867347	-0.602	0.957	N	0.522	0.403	0.381746406553	gnomAD-2.1.1	3.59E-05	None	None	None	None	N	None	0	0	None	0	5.16369E-04	None	0	None	0	0	0
K/T	rs766867347	-0.602	0.957	N	0.522	0.403	0.381746406553	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92308E-04	None	0	0	0	0	0
K/T	rs766867347	-0.602	0.957	N	0.522	0.403	0.381746406553	gnomAD-4.0.0	6.81976E-06	None	None	None	None	N	None	0	0	None	0	2.45371E-04	None	0	0	0	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
K/A	0.774	likely_pathogenic	0.7166	pathogenic	-0.437	Destabilizing	0.98	D	0.519	neutral	None	None	None	None	N
K/C	0.9174	likely_pathogenic	0.9052	pathogenic	-0.593	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
K/D	0.8639	likely_pathogenic	0.8142	pathogenic	-0.419	Destabilizing	0.997	D	0.515	neutral	None	None	None	None	N
K/E	0.4316	ambiguous	0.3378	benign	-0.351	Destabilizing	0.917	D	0.526	neutral	N	0.493423721	None	None	N
K/F	0.9623	likely_pathogenic	0.954	pathogenic	-0.442	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
K/G	0.7862	likely_pathogenic	0.7491	pathogenic	-0.756	Destabilizing	0.99	D	0.523	neutral	None	None	None	None	N
K/H	0.5617	ambiguous	0.4867	ambiguous	-1.226	Destabilizing	0.998	D	0.558	neutral	None	None	None	None	N
K/I	0.8117	likely_pathogenic	0.7702	pathogenic	0.365	Stabilizing	0.969	D	0.646	neutral	None	None	None	None	N
K/L	0.7545	likely_pathogenic	0.7027	pathogenic	0.365	Stabilizing	0.588	D	0.523	neutral	None	None	None	None	N
K/M	0.6349	likely_pathogenic	0.5642	pathogenic	0.425	Stabilizing	0.997	D	0.559	neutral	D	0.529000519	None	None	N
K/N	0.6919	likely_pathogenic	0.6138	pathogenic	-0.401	Destabilizing	0.996	D	0.479	neutral	N	0.509374608	None	None	N
K/P	0.9037	likely_pathogenic	0.8985	pathogenic	0.128	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
K/Q	0.2492	likely_benign	0.2052	benign	-0.621	Destabilizing	0.94	D	0.508	neutral	N	0.501792488	None	None	N
K/R	0.0941	likely_benign	0.0923	benign	-0.486	Destabilizing	0.009	N	0.217	neutral	N	0.452827892	None	None	N
K/S	0.7765	likely_pathogenic	0.7178	pathogenic	-1.009	Destabilizing	0.99	D	0.487	neutral	None	None	None	None	N
K/T	0.508	ambiguous	0.4189	ambiguous	-0.755	Destabilizing	0.957	D	0.522	neutral	N	0.50920125	None	None	N
K/V	0.765	likely_pathogenic	0.7219	pathogenic	0.128	Stabilizing	0.93	D	0.525	neutral	None	None	None	None	N
K/W	0.9302	likely_pathogenic	0.913	pathogenic	-0.339	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/Y	0.884	likely_pathogenic	0.8581	pathogenic	0.025	Stabilizing	0.98	D	0.601	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.