NM_000264.5(PTCH1):c.1177G>A (p.Ala393Thr) AND Holoprosencephaly 7

Germline classification:: Benign (2 submissions)
Last evaluated:: Apr 27, 2017
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000008704.8

Allele description [Variation Report for NM_000264.5(PTCH1):c.1177G>A (p.Ala393Thr)]

NM_000264.5(PTCH1):c.1177G>A (p.Ala393Thr)

Gene:

PTCH1:patched 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000264.5(PTCH1):c.1177G>A (p.Ala393Thr)

HGVS:

NC_000009.12:g.95479038C>T
NG_007664.1:g.42928G>A
NM_000264.5:c.1177G>AMANE SELECT
NM_001083602.3:c.979G>A
NM_001083603.3:c.1174G>A
NM_001083604.3:c.724G>A
NM_001083605.3:c.724G>A
NM_001083606.3:c.724G>A
NM_001083607.3:c.724G>A
NM_001354918.2:c.1177G>A
NP_000255.2:p.Ala393Thr
NP_001077071.1:p.Ala327Thr
NP_001077072.1:p.Ala392Thr
NP_001077073.1:p.Ala242Thr
NP_001077074.1:p.Ala242Thr
NP_001077075.1:p.Ala242Thr
NP_001077076.1:p.Ala242Thr
NP_001341847.1:p.Ala393Thr
LRG_515t1:c.1177G>A
LRG_515:g.42928G>A
NC_000009.11:g.98241320C>T
NM_000264.3:c.1177G>A
NR_149061.2:n.2082G>A
Q13635:p.Ala393Thr

Protein change:

A242T; ALA393THR

Links:

UniProtKB: Q13635#VAR_032952; OMIM: 601309.0011; dbSNP: rs199476091

NCBI 1000 Genomes Browser:

rs199476091

Molecular consequence:

NM_000264.5:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083602.3:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083603.3:c.1174G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083604.3:c.724G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083605.3:c.724G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083606.3:c.724G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083607.3:c.724G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354918.2:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_149061.2:n.2082G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Holoprosencephaly 7 (HPE7)
Identifiers:: MONDO: MONDO:0012562; MedGen: C1835820; Orphanet: 2162; OMIM: 610828

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S41 family peptidase [Oceanobacillus jeddahense]
S41 family peptidase [Oceanobacillus jeddahense]
gi|2281275012|gnl|PRJNA607328|NP439 5|gb|UUI02137.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028913	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001332159	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11941477, 19346217 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028913

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2002)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV001332159

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly.

Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M.

Hum Genet. 2002 Apr;110(4):297-301. Epub 2002 Mar 2. Erratum in: Hum Genet 2002 Oct;111(4-5):464.

PubMed [citation]

PMID:: 11941477

Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function.

Lacbawan F, Solomon BD, Roessler E, El-Jaick K, Domené S, Vélez JI, Zhou N, Hadley D, Balog JZ, Long R, Fryer A, Smith W, Omar S, McLean SD, Clarkson K, Lichty A, Clegg NJ, Delgado MR, Levey E, Stashinko E, Potocki L, Vanallen MI, et al.

J Med Genet. 2009 Jun;46(6):389-98. doi: 10.1136/jmg.2008.063818. Epub 2009 Apr 2.

PubMed [citation]

PMID:: 19346217
PMCID:: PMC3510661

Details of each submission

From OMIM, SCV000028913.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a female with holoprosencephaly (HPE7; 610828), Ming et al. (2002) identified a heterozygous 1165G-A transition in the PTCH gene, resulting in an ala393-to-thr (A393T) substitution in an extracellular loop of the PTCH protein. The variant was also present in her clinically normal father.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001332159.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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