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NM_001317778.2(SFTPC):c.202G>T (p.Val68Phe) AND Hereditary pulmonary alveolar proteinosis

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 7, 2021
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:
RCV002423012.1

Allele description [Variation Report for NM_001317778.2(SFTPC):c.202G>T (p.Val68Phe)]

NM_001317778.2(SFTPC):c.202G>T (p.Val68Phe)

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.202G>T (p.Val68Phe)
HGVS:
  • NC_000008.11:g.22163080G>T
  • NG_016968.1:g.6410G>T
  • NG_029659.1:g.2941G>T
  • NM_001172357.2:c.202G>T
  • NM_001172410.2:c.202G>T
  • NM_001317778.2:c.202G>TMANE SELECT
  • NM_001317779.2:c.43G>T
  • NM_001317780.2:c.202G>T
  • NM_001385653.1:c.202G>T
  • NM_001385654.1:c.202G>T
  • NM_001385655.1:c.202G>T
  • NM_001385656.1:c.202G>T
  • NM_001385657.1:c.202G>T
  • NM_001385658.1:c.202G>T
  • NM_001385659.1:c.202G>T
  • NM_001385660.1:c.43G>T
  • NM_003018.4:c.202G>T
  • NP_001165828.1:p.Val68Phe
  • NP_001165881.1:p.Val68Phe
  • NP_001304707.1:p.Val68Phe
  • NP_001304708.1:p.Val15Phe
  • NP_001304709.1:p.Val68Phe
  • NP_001372582.1:p.Val68Phe
  • NP_001372583.1:p.Val68Phe
  • NP_001372584.1:p.Val68Phe
  • NP_001372585.1:p.Val68Phe
  • NP_001372586.1:p.Val68Phe
  • NP_001372587.1:p.Val68Phe
  • NP_001372588.1:p.Val68Phe
  • NP_001372589.1:p.Val15Phe
  • NP_003009.2:p.Val68Phe
  • NC_000008.10:g.22020593G>T
  • NM_003018.3:c.202G>T
Protein change:
V15F
Links:
dbSNP: rs2131816806
NCBI 1000 Genomes Browser:
rs2131816806
Molecular consequence:
  • NM_001172357.2:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001172410.2:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317778.2:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317779.2:c.43G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317780.2:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385653.1:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385654.1:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385655.1:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385656.1:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385657.1:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385658.1:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385659.1:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385660.1:c.43G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003018.4:c.202G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002718707Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Likely pathogenic
(May 7, 2021) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene.

Stevens PA, Pettenazzo A, Brasch F, Mulugeta S, Baritussio A, Ochs M, Morrison L, Russo SJ, Beers MF.

Pediatr Res. 2005 Jan;57(1):89-98. Epub 2004 Nov 19.

PubMed [citation]
PMID:
15557112

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

Details of each submission

From Ambry Genetics, SCV002718707.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.V68F variant (also known as c.202G>T) is located in coding exon 3 of the SFTPC gene. The valine at codon 68 is replaced by phenylalanine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 3. This variant was noted as an interstitial lung disease mutation and was identified in an infant; specific clinical information was not provided (Willander H et al. Proc Natl Acad Sci U S A, 2012 Feb;109:2325-9). In our internal cohort, this variant has been determined to be the result of a de novo mutation or germline mosaicism in one family with an isolated case of respiratory failure and interstitial lung disease (Ambry internal data). Based on internal structural analysis, V68F disrupts a conserved position in a motif responsible for stabilizing BRICHOS-substrate interactions in SFTPC (Stevens PA et al. Pediatr Res, 2005 Jan;57:89-98; Willander H et al. Proc Natl Acad Sci U S A, 2012 Feb;109:2325-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Feb 20, 2024