TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15116	45571;45572;45573	chr2:178621478;178621477;178621476	chr2:179486205;179486204;179486203
N2AB	13475	40648;40649;40650	chr2:178621478;178621477;178621476	chr2:179486205;179486204;179486203
N2A	12548	37867;37868;37869	chr2:178621478;178621477;178621476	chr2:179486205;179486204;179486203
N2B	6051	18376;18377;18378	chr2:178621478;178621477;178621476	chr2:179486205;179486204;179486203
Novex-1	6176	18751;18752;18753	chr2:178621478;178621477;178621476	chr2:179486205;179486204;179486203
Novex-2	6243	18952;18953;18954	chr2:178621478;178621477;178621476	chr2:179486205;179486204;179486203
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-102
• Domain position: 86
• Structural Position: 178
• Q(SASA): 0.9609
• Predicted PPI site: I

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
H/R	rs1413491989	0.054	0.213	N	0.208	0.207	0.258283824007	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
H/R	rs1413491989	0.054	0.213	N	0.208	0.207	0.258283824007	gnomAD-4.0.0	3.42425E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00019E-07	4.64145E-05	0
H/Y	None	None	0.523	N	0.257	0.111	0.288727942641	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
H/A	0.2899	likely_benign	0.3248	benign	0.121	Stabilizing	0.228	N	0.235	neutral	None	None	None	None	I
H/C	0.2193	likely_benign	0.287	benign	0.648	Stabilizing	0.983	D	0.205	neutral	None	None	None	None	I
H/D	0.2274	likely_benign	0.2746	benign	-0.186	Destabilizing	0.101	N	0.251	neutral	N	0.485758781	None	None	I
H/E	0.27	likely_benign	0.3119	benign	-0.147	Destabilizing	0.129	N	0.239	neutral	None	None	None	None	I
H/F	0.3275	likely_benign	0.3631	ambiguous	0.936	Stabilizing	0.716	D	0.294	neutral	None	None	None	None	I
H/G	0.3293	likely_benign	0.3604	ambiguous	-0.181	Destabilizing	0.129	N	0.253	neutral	None	None	None	None	I
H/I	0.2739	likely_benign	0.3433	ambiguous	0.904	Stabilizing	0.264	N	0.319	neutral	None	None	None	None	I
H/K	0.1958	likely_benign	0.2079	benign	0.029	Stabilizing	0.001	N	0.142	neutral	None	None	None	None	I
H/L	0.1144	likely_benign	0.1281	benign	0.904	Stabilizing	0.001	N	0.187	neutral	D	0.56666123	None	None	I
H/M	0.4154	ambiguous	0.4729	ambiguous	0.658	Stabilizing	0.716	D	0.21	neutral	None	None	None	None	I
H/N	0.0748	likely_benign	0.0867	benign	-0.002	Destabilizing	None	N	0.092	neutral	N	0.490802684	None	None	I
H/P	0.4759	ambiguous	0.4407	ambiguous	0.668	Stabilizing	0.794	D	0.305	neutral	D	0.56666123	None	None	I
H/Q	0.1467	likely_benign	0.1585	benign	0.14	Stabilizing	0.351	N	0.251	neutral	N	0.488363935	None	None	I
H/R	0.0941	likely_benign	0.0979	benign	-0.617	Destabilizing	0.213	N	0.208	neutral	N	0.440553411	None	None	I
H/S	0.1943	likely_benign	0.2248	benign	0.137	Stabilizing	0.129	N	0.26	neutral	None	None	None	None	I
H/T	0.2094	likely_benign	0.2549	benign	0.276	Stabilizing	0.228	N	0.239	neutral	None	None	None	None	I
H/V	0.2304	likely_benign	0.2812	benign	0.668	Stabilizing	0.264	N	0.271	neutral	None	None	None	None	I
H/W	0.4293	ambiguous	0.4848	ambiguous	0.973	Stabilizing	0.983	D	0.222	neutral	None	None	None	None	I
H/Y	0.1105	likely_benign	0.1253	benign	1.187	Stabilizing	0.523	D	0.257	neutral	N	0.493840564	None	None	I

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.