NM_001317778.2(SFTPC):c.176A>G (p.His59Arg) AND Hereditary pulmonary alveolar proteinosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 2, 2019
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:: RCV002402077.2

Allele description [Variation Report for NM_001317778.2(SFTPC):c.176A>G (p.His59Arg)]

NM_001317778.2(SFTPC):c.176A>G (p.His59Arg)

Gene:

SFTPC:surfactant protein C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p21.3

Genomic location:

Preferred name:

NM_001317778.2(SFTPC):c.176A>G (p.His59Arg)

Other names:

p.His59Arg

HGVS:

NC_000008.11:g.22162707A>G
NG_016968.1:g.6037A>G
NG_029659.1:g.2568A>G
NM_001172357.2:c.176A>G
NM_001172410.2:c.176A>G
NM_001317778.2:c.176A>GMANE SELECT
NM_001317779.2:c.43-373A>G
NM_001317780.2:c.176A>G
NM_003018.4:c.176A>G
NP_001165828.1:p.His59Arg
NP_001165881.1:p.His59Arg
NP_001304707.1:p.His59Arg
NP_001304709.1:p.His59Arg
NP_003009.2:p.His59Arg
NC_000008.10:g.22020220A>G
NC_000008.10:g.22020220A>G
NM_003018.3:c.176A>G

Protein change:

H59R

Links:

dbSNP: rs201567623

NCBI 1000 Genomes Browser:

rs201567623

Molecular consequence:

NM_001317779.2:c.43-373A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001172357.2:c.176A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001172410.2:c.176A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317778.2:c.176A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317780.2:c.176A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003018.4:c.176A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary pulmonary alveolar proteinosis
Synonyms:: Pulmonary surfactant metabolism dysfunction
Identifiers:: MONDO: MONDO:0012580; MedGen: C3711368; OMIM: PS265120

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002713403	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 2, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22308375, 25657025, 27362365 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002713403

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 2, 2019)

germline

clinical testing

PubMed (3)
[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

Citations

PubMed

High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C.

Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, Keränen H, Hermansson E, Hamvas A, Nogee LM, Bergman T, Saenz A, Casals C, Åqvistg J, Jörnvall H, Berglund H, Presto J, Knight SD, Johansson J.

Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2325-9. doi: 10.1073/pnas.1114740109. Epub 2012 Feb 2.

PubMed [citation]

PMID:: 22308375
PMCID:: PMC3289314

Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients.

Kröner C, Reu S, Teusch V, Schams A, Grimmelt AC, Barker M, Brand J, Gappa M, Kitz R, Kramer BW, Lange L, Lau S, Pfannenstiel C, Proesmans M, Seidenberg J, Sismanlar T, Aslan AT, Werner C, Zielen S, Zarbock R, Brasch F, Lohse P, et al.

Eur Respir J. 2015 Jul;46(1):197-206. doi: 10.1183/09031936.00129414. Epub 2015 Feb 5.

PubMed [citation]

PMID:: 25657025

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002713403.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.H59R variant (also known as c.176A>G), located in coding exon 2 of the SFTPC gene, results from an A to G substitution at nucleotide position 176. The histidine at codon 59 is replaced by arginine, an amino acid with highly similar properties. In one study, this variant was detected in trans with a second SFTPC alteration in a female with onset of symptoms at birth (Willander H et al. Proc. Natl. Acad. Sci. U.S.A., 2012 Feb;109:2325-9). In addition, this variant was identified in an individual with combined pulmonary fibrosis and emphysema syndrome with onset of symptoms at age 11 years; this individual's healthy father was also heterozygous for the variant (Kröner C et al. Eur. Respir. J., 2015 Jul;46:197-206). In our internal cohort, this variant was observed in the homozygous state in a proband exhibiting surfactant deficiency on lung biopsy; parental testing revealed that both of the unaffected parents were heterozygous. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this alteration remains unclear.

#	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: Sep 29, 2024

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