TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33408	100447;100448;100449	chr2:178536525;178536524;178536523	chr2:179401252;179401251;179401250
N2AB	31767	95524;95525;95526	chr2:178536525;178536524;178536523	chr2:179401252;179401251;179401250
N2A	30840	92743;92744;92745	chr2:178536525;178536524;178536523	chr2:179401252;179401251;179401250
N2B	24343	73252;73253;73254	chr2:178536525;178536524;178536523	chr2:179401252;179401251;179401250
Novex-1	24468	73627;73628;73629	chr2:178536525;178536524;178536523	chr2:179401252;179401251;179401250
Novex-2	24535	73828;73829;73830	chr2:178536525;178536524;178536523	chr2:179401252;179401251;179401250
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-131
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1191
• 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
S/C	rs1268223494	-0.995	1.0	N	0.814	0.521	0.554920031903	gnomAD-2.1.1	5.51E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.13E-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
S/A	0.1293	likely_benign	0.1169	benign	-0.495	Destabilizing	0.997	D	0.46	neutral	N	0.476633294	None	None	N
S/C	0.1806	likely_benign	0.1637	benign	-0.707	Destabilizing	1.0	D	0.814	deleterious	N	0.48820709	None	None	N
S/D	0.7326	likely_pathogenic	0.7899	pathogenic	-1.488	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
S/E	0.7572	likely_pathogenic	0.8171	pathogenic	-1.445	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	N
S/F	0.3069	likely_benign	0.3162	benign	-0.711	Destabilizing	1.0	D	0.875	deleterious	N	0.495030718	None	None	N
S/G	0.1476	likely_benign	0.1373	benign	-0.752	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	N
S/H	0.5393	ambiguous	0.5808	pathogenic	-1.298	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
S/I	0.4312	ambiguous	0.4647	ambiguous	0.089	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
S/K	0.8988	likely_pathogenic	0.9334	pathogenic	-0.723	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
S/L	0.2226	likely_benign	0.2273	benign	0.089	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
S/M	0.3722	ambiguous	0.3417	ambiguous	0.311	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
S/N	0.2748	likely_benign	0.3096	benign	-1.042	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
S/P	0.9913	likely_pathogenic	0.9942	pathogenic	-0.072	Destabilizing	1.0	D	0.832	deleterious	D	0.525807951	None	None	N
S/Q	0.719	likely_pathogenic	0.7636	pathogenic	-1.204	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
S/R	0.829	likely_pathogenic	0.8883	pathogenic	-0.637	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/T	0.1316	likely_benign	0.1202	benign	-0.82	Destabilizing	0.999	D	0.471	neutral	D	0.527682649	None	None	N
S/V	0.4441	ambiguous	0.4428	ambiguous	-0.072	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
S/W	0.6547	likely_pathogenic	0.6803	pathogenic	-0.842	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
S/Y	0.3076	likely_benign	0.3375	benign	-0.466	Destabilizing	1.0	D	0.881	deleterious	N	0.484635464	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.